Precision Medicine Communications
type: channel
description: Precision Medicine Communications is a biannual, peer-reviewed, open-access, print and electronic journal dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. It especially considers studies investigating the effects of genetic variability on drug toxicity and efficacy, identification and functional characterization of polymorphisms relevant to the pharmacological action and adverse effects of a drug, integration of new developments in the genome project, and proteomics into clinical medicine, pharmacology, and therapeutics, clinical implementation of pharmacogenomics, identification of novel genomic targets for drug development, economics of genome-guided interventions, clinical implementation of pharmacogenomics, pharmacogenomics in developing countries, companion diagnostics and drug development.
publisher: Roots Press
language: en
publication name: Precision Medicine Communications
issn: 2958-5821
items: Single Nucleotide Polymorphisms as Genetic Determinants of Azathioprine Efficacy & Toxicity
items: Efficacy of the Angiotensin-Converting Enzyme Inhibitors in a Pakistani Hypertensive Cohort and its Associations with Genetic Variation in SCLO1B1 Gene
items: Drug Repurposing of Loratadine as a DNMT1 Inhibitor: Comparative Evaluation with Cisplatin in Patient-Derived Oral Squamous Cell Carcinoma Cells
items: Escitalopram Pharmacogenetics: What Does the Evidence Suggest?
items: Treatment Response to Sertraline in the Pakistani Population and its Association with Cytochrome P450 2C19 Genotypes
items: Genetic Variation in CYP2D6 and Adverse Effects in Cardiovascular Patients on Metoprolol Therapy
items: Pharmacogenomics of Prostate Cancer: A Review of Recent Progress in Diagnosis, Personalized Medicine and Future Challenges
items: Atorvastatin Pharmacogenetics: What is the Evidence for Genetic Association with Efficacy & Safety?
items: Treatment Response to Sorafenib in Liver Cancer; A Comprehensive Review on Association with Single Nucleotide Polymorphisms
items: Genetic Polymorphism in CYP3A4 and CYP3A5 Genes and their Association with the Clinical Response to Calcineurin Inhibitors; A Narrative Review
items: Editor's Summaries of the Articles Published in This Issue of Precision Medicine Communications
items: Rapid & Low-Cost DPYD Genotyping to Guide Fluoropyrimidine Treatment in Cancer Patients
items: Pharmacogenomic Variants Affecting Statins Response in Sri Lanka
items: Prediction of PEGylated INF-α Treatment Response in Hepatitis B Patients
items: TREX1 Mutations in Aicardi–Goutières Syndrome with Congenital Glaucoma
items: Predictors of Voriconazole Concentration in Hematopoietic Stem Cell Transplant
items: Role of Microbiome in Personalized Medicine
items: Association of GABRG2 rs211037 Gene Polymorphism With Epilepsies and Pharmacoresistance to Anti-Epileptic Drugs; A Meta-Analysis
items: Integrative Investigation and Prioritization of Candidate Genes PTGS-2 and VEGF: Unveiling their Interaction with Celecoxib for Targeted Therapeutic Applications
items: Investigation of the Association of GATM Gene Polymorphisms with Statin-Induced Myopathy
items: Pharmacogenomics of Leukemia; Unlocking Personalized Treatment Strategies
items: Pharmacogenetics of Tacrolimus in Solid Organ Transplant Patients
items: Impact of CYP3A5 Genotype on De-novo LCP Tacrolimus Dosing in Kidney Transplantation
items: Genetic Polymorphism & Methotrexate Therapy Outcomes in Rheumatoid Arthritis
items: Genetic Variation in OPRK1 Gene and Opioid Use Disorder
items: Side Effects and Genetic Variation During Depression in Taiwanese Han Population
items: Pregnane X Receptor Gene Variation and Total Mortality in Nonalcoholic Fatty Liver Disease
items: Precision Medicine Approaches for Psychosis Treatment
items: Exploring the Potential of Drug Repurposing: Detection of Cystic Fibrosis Transmembrane Conductance Regulator as a Biomarker in Breast Cancer Patients

Single Nucleotide Polymorphisms as Genetic Determinants of Azathioprine Efficacy & Toxicity
type: item
description: Azathioprine (AZA) is among the most widely prescribed immunosuppressive agents of the past five decades. It finds its application in organ transplantation therapy, autoimmune disorders, and various inflammatory conditions. However, its therapeutic efficacy is often marred by unwanted side effects or adverse drug reactions (ADRs). Polymorphism in genes like thiopurine methyltransferase (TPMT), inosine triphosphate pyrophosphatase (ITPA), nudix hydrolase 15 (NUDT15), and later influences on enzymatic activity play a crucial role in modulating AZA's response and toxicity. Additionally, racial, and ethnic factors further complicate the metabolic outcome of this drug. These changes can lead to undesirable outcomes like myelotoxicity, hematopoietic toxicity, neutropenia, and leukocytopenia. Due to the unpredictability of AZA outcomes, elicited by genetic variations, the Food and Drug Administration (FDA) has recommended genetic screening prior to AZA therapy initiation, highlighting the move towards precision medicine. While pharmacogenetic screening is recommended, accessibility, cost, and ethical considerations are still hurdles in its implementation. This review explores deep into the studies and literature available, reporting the intricate interaction between single nucleotide polymorphisms (SNPs) and the resulting impact on AZA efficacy. The article also recommends how to effectively use pharmacogenetic tools for improving its usage. By incorporating genetic information in treatment plans involving AZA, a patient-centered approach can be achieved, potentially improving the efficacy, safety, and cost-effectiveness of AZA therapy.
subject: Review Articles
  topic: section
subject: Genetic variation
  topic: keywords
subject: Azathioprine
  topic: keywords
subject: adverse effects
  topic: keywords
subject: efficacy
  topic: keywords
subject: genetic polymorphism
  topic: keywords
creator: Nida Saleem
creator: Anina Qureshi
rights: Copyright (c) 2025 Nida Saleem, Anina Qureshi https://creativecommons.org/licenses/by/4.0
date: 2024-12-30
publication date: 2024-12-30
starting page: 63
ending page: 83
doi: 10.55627/pmc.004.02.1214

Efficacy of the Angiotensin-Converting Enzyme Inhibitors in a Pakistani Hypertensive Cohort and its Associations with Genetic Variation in SCLO1B1 Gene
type: item
description: A significant proportion of individuals at high risk of cardiovascular risks are prescribed Angiotensin-converting enzyme inhibitors (ACEIs). This study investigated the potential link between SLCO1B1 genetic variations and the effectiveness of ACEIs in managing hypertension within a Pakistani cohort. Designed as a prospective cohort study, it was conducted at a tertiary care hospital, enrolling 83 patients through a convenient sampling approach. After informed consent, 2 mL of blood was withdrawn from each participant. After the DNA extraction from blood samples, single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene were determined through partial sequencing. Furthermore, a structured questionnaire was employed to gather data. The findings indicated a notable reduction in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) following two weeks of ACEI therapy. However, no significant correlation was detected between ACEI efficacy and the two SNPs examined in this population. Expanding this research to larger and more genetically diverse cohorts could provide a clearer understanding of the association between genetic variants and ACEI therapeutic response.
subject: Research Articles
  topic: section
subject: Angiotensin converting enzyme
  topic: keywords
subject: hypertension
  topic: keywords
subject: genetic polymorphism
  topic: keywords
subject: SCLO1B1
  topic: keywords
subject: therapeutic response
  topic: keywords
creator: Fawad Ali
creator: Taseer Ahmad
rights: Copyright (c) 2024 Fatima Siraj https://creativecommons.org/licenses/by/4.0
date: 2024-12-30
publication date: 2024-12-30
starting page: 115
ending page: 123
doi: 10.55627/pmc.004.02.1084

Drug Repurposing of Loratadine as a DNMT1 Inhibitor: Comparative Evaluation with Cisplatin in Patient-Derived Oral Squamous Cell Carcinoma Cells
type: item
description: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with a low overall survival rate due to altered epigenetic regulation, specifically DNA hypermethylation mediated by DNA methyltransferase 1 (DNMT1). Inhibitors of DNMT1 are promising compounds for cancer treatment and research. In this study, repurposed drugs, including Loratadine, were virtually screened through molecular docking to select the drug with the highest interaction with the DNMT1 protein. Loratadine demonstrated maximum drug-like characteristics, making it a promising treatment option for OSCC patients. Furthermore, for experimental validation, we investigated the cytotoxicity of Loratadine, Cisplatin, and their combination against primary oral squamous cell carcinoma cells. The MTT assays revealed that Loratadine and Cisplatin each had a time and dose-dependent inhibitory impact, with 50% inhibitory concentrations (IC50) of 86.78 µM and 67.05 µM, respectively. The combination of both drugs had an additive effect against OSCC cells, with an IC50 of 52.05 µM. However, the apoptosis assay results revealed that treatment with loratadine had no significant effect on cell viability in OSCC. These findings suggest that Loratadine likely has anti-cancer effects but kills or inhibits cells at various dosages, independently of apoptosis. Further mechanistic studies are needed.
subject: Research Articles
  topic: section
subject: Loratadine
  topic: keywords
subject: cisplatin
  topic: keywords
subject: drug repurposing
  topic: keywords
subject: OSSC
  topic: keywords
subject: DNMT1
  topic: keywords
subject: Molecular Docking
  topic: keywords
creator: Nooria Siddiqui
creator: Aiman Shoaib
creator: Ubaid Khan
creator: Muhammad Zubair
creator: Shafaq Zafar
rights: Copyright (c) 2024 Inzemam Haq https://creativecommons.org/licenses/by/4.0
date: 2024-12-30
publication date: 2024-12-30
starting page: 125
ending page: 137
doi: 10.55627/pmc.004.02.1083

Escitalopram Pharmacogenetics: What Does the Evidence Suggest?
type: item
description: Depression is among the most diagnosed mental health conditions. It affects how a person thinks, feels, and behaves. It can impact anyone at any age and deprive one of physical and emotional life force. In the post-COVID-19 world, depression has become even more prevalent and pervasive. While scientists are actively trying to track the pathophysiology of depression, for now, it remains to be fully understood. Escitalopram, the enantiomer of citalopram, is widely prescribed for treating anxiety, depression, obsessive-compulsive disorder (OCD), etc. It is a potent selective serotonin reuptake inhibitor (SSRI), but its effect is varied in different individuals, as therapeutic failures are common with antidepressants. Pharmacogenomics can help with tailoring effective therapeutic strategies by defining biomarkers to classify responders and non-responders, minimizing the risk of side effects and adverse events. For escitalopram, genes like SCL6A4 rs25531, ABCB1 rs1045642, and CYP2C19*17 rs12248560 were associated with optimal therapeutic response, with better remission rates at lower doses. These findings can be utilized for curating effective patient-centric therapeutic strategies.
subject: Review Articles
  topic: section
subject: Depression
  topic: keywords
subject: escitalopram
  topic: keywords
subject: SSRI
  topic: keywords
subject: pharmacogenetics
  topic: keywords
subject: personalized medicine
  topic: keywords
creator: Nida Saleem
creator: Naim Ul Huda
rights: Copyright (c) 2024 Fawad Bangash https://creativecommons.org/licenses/by/4.0
date: 2025-06-30
publication date: 2025-06-30
starting page: 19
ending page: 37
doi: 10.55627/pmc.004.02.0778

Treatment Response to Sertraline in the Pakistani Population and its Association with Cytochrome P450 2C19 Genotypes
type: item
description: Selective serotonin reuptake inhibitors (SSRIs) are metabolized differently depending on variations in the CYP2C19 gene. Clinical practitioners are using pharmacogenetic information based on the impact of CYP2C19 polymorphisms more frequently. Yet, the fundamental tenets connecting distinct metabolism to efficacy or adverse drug reactions are still poorly understood. This research was conducted in the hopes of establishing a link between genetic variants of the CYP2C19 gene and the therapeutic effect and adverse effects of the antidepressant Sertraline. The objective of this study was to determine the CYP2C19*2, *3, and *17 allele and genotype frequencies among the treatment-responsive and resistant patients and their correlation with the response and to determine the association of CYP2C19 allele to adverse effects of sertraline in major depressive disorder (MDD) patients. The study was conducted at the Institute of Pharmaceutical Sciences, Khyber Medical University. Fifty patients of MDD were recruited from a psychiatric clinic to take part in this study. Three scales, Hamilton Depression Rating Scale (HDRS or HAMD-17), General Medication Adherence Scale (GMAS), and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) were used to assess depression severity, adherence to drug therapy, and adverse effects respectively at baseline and then at weeks 2, 4, 6 and finally at 6 months. 3ml blood was also taken from patients for genotyping polymorphic variants of CYP2C19. We found that the risk factors for depression as indicated by our study are females (58%) OR 1.18 as compared to males OR 0.75, married individuals (74%), and poor socioeconomic status (40%). A high response rate to sertraline was recorded with 82% responders and only 18% non-responders. Response rate of males was slightly higher than females at 92% and 90% respectively. HAMD 1st follow-up was significantly correlated to baseline score at p-value 0.01. GMAS was negatively correlated to HAM…
subject: Research Articles
  topic: section
subject: Sertraline
  topic: keywords
subject: CYP2C19
  topic: keywords
subject: major depressive disorder
  topic: keywords
subject: depression
  topic: keywords
subject: genetic variation
  topic: keywords
subject: single nucleotide polymorphism
  topic: keywords
creator: Hareem Zarghuna Khan
creator: Zafar Sadiq
creator: Imran Khan
creator: Muhammad Ali
rights: Copyright (c) 2024 Hareem Zarghuna Khan, Zafar Sadiq, Imran Khan, Muhammad Ali https://creativecommons.org/licenses/by/4.0
date: 2024-06-29
publication date: 2024-06-29
starting page: 51
ending page: 61
doi: 10.55627/pmc.004.001.0777

Genetic Variation in CYP2D6 and Adverse Effects in Cardiovascular Patients on Metoprolol Therapy
type: item
description: The CYP2D6 genetic variation seems to be important for several clinically used drugs including metoprolol. The frequency of adverse effects of metoprolol may vary depending upon the genotype of CYP2D6. However, how CYP2D6 genetic variation affects metoprolol's adverse effects is not well understood in the Pakistani population. In this study, we prospectively included Pakistani patients who started metoprolol treatment for cardiovascular indications. Decisions on inclusion and exclusion were made without awareness of the CYP2D6 genotype. Before intake of the first metoprolol dose, detailed medical history, baseline clinical characteristics, and laboratory indices were obtained. For CYP2D6 polymorphism examination, 5 ml of venous blood was collected and stored in a −80°C refrigerator until analysis. This study was approved by the Ethics Board of the Kohat University of Science & Technology and was conducted in line with the ethical guidelines of the 1975 Declaration of Helsinki. Our results showed that all the patients were wild type for this CYP2D6*6 (rs5030655) and no variant allele was found. For CYP2D6*4(rs1065852), 60 patients were wild type, 27 were heterozygous and only 3 patients were homozygous mutants for this single nucleotide polymorphism. Dizziness, bradycardia, and hypotension were more frequently observed adverse effects than lightheadedness and syncope. The frequency of adverse effects was hypotension (20), bradycardia (21), lightheadedness (16), dizziness (45), and syncope (13). The distribution of adverse effects in different genotypes of CYP2D6*4(rs1065852) reveals that this genetic variation is not associated with the adverse effects experienced by metoprolol users in a Pakistani cohort with cardiovascular indications.
subject: Research Articles
  topic: section
subject: CYP2D6
  topic: keywords
subject: metoprolol
  topic: keywords
subject: genetic variants
  topic: keywords
subject: adverse effects
  topic: keywords
subject: single nucleotide polymorphism
  topic: keywords
creator: Mehwish Rafique
creator: Ayesha Nasir
creator: Nida Saleem
rights: Copyright (c) 2024 Mehwish Rafique, Ayesha Nasir, Nida Saleem https://creativecommons.org/licenses/by/4.0
date: 2024-06-29
publication date: 2024-06-29
starting page: 41
ending page: 49
doi: 10.55627/pmc.004.001.0776

Pharmacogenomics of Prostate Cancer: A Review of Recent Progress in Diagnosis, Personalized Medicine and Future Challenges
type: item
description: Prostate adenocarcinoma, in men, is the fifth leading cause of cancer casualties. Prostate cancer (PCa) is slow-growing with relatively low-grade aggressiveness. The prostate gland in the male reproductive system synthesizes and stores semen and seminal fluid. It sits inferior to the bladder, surrounds the superior part of the urethra and anterior to the rectum, and weighs approximately 20g in adult men. The prostate contains numerous small glands that produce 20% of the seminal fluid. In PCa, the cells of these glands undergo a malignant transformation and become cancerous. Single nucleotide polymorphisms (SNPs) are the most common type of gene variation, and many SNPs are associated with PCa risk. SNPs are small mutations in DNA sequences that can alter the structure and function of proteins. They are often inherited from parents and can vary frequently among different populations. SNPs in candidate genes, such as those involved in cell growth and differentiation, have been proven to increase susceptibility to prostate adenocarcinoma. Identifying SNPs linked with PCa risk can potentially upgrade early detection and disease prevention. The research on SNPs in PCa is still in its early stages. However, the findings to date suggest that SNPs have the potential to be valuable tools for the advancement of the diagnosis, prevention, and treatment of this devastating disease. For instance, rs6983267 and rs1447295 at the 8q24 gene in Caucasians and Asians have a strong association with prostate adenocarcinoma. In contrast, rs16901979 in the same gene in African Americans has shown a significant association with prostate malignancy. Meanwhile, in the European population, rs138213197 has a notable association with PCa. In addition to the association with the disease, SNPs may also be involved in treatment failure or toxicities in patients battling prostate carcinoma. For example, in the English population, rs4646487 CYP4B1 and rs2227291 ATP7A are responsible for toxicities …
subject: Review Articles
  topic: section
subject: Prostate cancer
  topic: keywords
subject: genetic polymorphism
  topic: keywords
subject: pharmacogenomics of prostate cancer
  topic: keywords
subject: prostate specific antigen
  topic: keywords
subject: next-generation sequencing
  topic: keywords
creator: Fawad Bashir
creator: Kinza Farooq
creator: Ayesha Irfan
rights: Copyright (c) 2024 Fawad Bashir, Kinza Farooq, Ayesha Irfan https://creativecommons.org/licenses/by/4.0
date: 2024-06-29
publication date: 2024-06-29
starting page: 03
ending page: 20
doi: 10.55627/pmc.004.001.0557

Atorvastatin Pharmacogenetics: What is the Evidence for Genetic Association with Efficacy & Safety?
type: item
description: Hyperlipidemia, characterized by elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and/or decreased high-density lipoprotein cholesterol (HDL-C), is a key contributor to the development of cardiovascular diseases (CVD), which remain the leading cause of morbidity and mortality worldwide. Statins, especially atorvastatin, are the mainstay pharmacological agents used to lower cholesterol levels and prevent atherosclerotic complications. Atorvastatin inhibits HMG-CoA reductase, reducing hepatic cholesterol synthesis and upregulating LDL receptor expression. However, the efficacy and safety of atorvastatin therapy are significantly influenced by genetic polymorphisms in drug-metabolizing enzymes, transporters, and lipid-regulating genes. This review comprehensively examines the pharmacogenetics of atorvastatin, focusing on genetic variants influencing drug absorption, distribution, metabolism, and pharmacodynamic response. Polymorphisms in hepatic uptake transporters (SLCO1B1), efflux transporters (ABCB1, ABCG2), drug-metabolizing enzymes (CYP3A4 and CYP3A5), and lipid-regulating genes (APOE, APOA5, APOB, LDLR) are critically evaluated across diverse populations. Among these, the SLCO1B1 c.521T>C (rs4149056) variant emerges as a key determinant of atorvastatin exposure and myopathy risk, though its clinical relevance varies by ethnicity. Pharmacogenetic studies show population-specific variations in atorvastatin outcomes, emphasizing the need for precision medicine in hyperlipidemia management.
subject: Review Articles
  topic: section
subject: Atorvastatin
  topic: keywords
subject: safety
  topic: keywords
subject: efficacy
  topic: keywords
subject: pharmacogenetics
  topic: keywords
subject: personalized medicine
  topic: keywords
creator: Nimra Riaz
creator: Madeeha Khan
rights: Copyright (c) 2024 Sagheer Ahmed https://creativecommons.org/licenses/by/4.0
date: 2025-06-30
publication date: 2025-06-30
starting page: 03
ending page: 17
doi: 10.55627/pmc.004.02.0556

Treatment Response to Sorafenib in Liver Cancer; A Comprehensive Review on Association with Single Nucleotide Polymorphisms
type: item
description: Liver cancer is one of the most challenging cancers to diagnose and treat. Sorafenib is a tyrosine kinase inhibitor (TKI) that is prescribed for advanced or unresectable liver cancer. While this drug is one of the already-limited choices for liver cancer treatment, sorafenib resistance and variation in therapeutic response add further to the difficulties in pharmacotherapy for liver cancers. There are various ways in which cancer cells can protect themselves from these drugs; genetic polymorphism is one of the ways through which the mechanisms of varied responses to sorafenib can be comprehended. Notably, studies including genes involved in pharmacokinetics of sorafenib like ATP binding cassette subfamily B member 1 (ABCB1 rs2032582, rs1045642), ATP binding cassette subfamily G member 2 (ABCG2 rs2231137, rs2231142, rs2622604), ATP binding cassette subfamily C member 2 (ABCC2/ MRP2 rs3740066), UDP glucuronosyltransferase family 1 member A1 (UGT1A1 rs8175347), UDP glucuronosyltransferase family 1 member A9 (UGT1A9 rs17868320, rs72551330, rs6714486), Cytochrome p450 system ( CYP3A5*3 rs776746), (CYP3A4 rs2740574), (CYP26A1 rs7905939), Solute carrier organic anion transporter family member 1 B1 (SLCO1B1 rs2306283, rs4149056), Solute carrier family 22 member 14 (SLC22A14 rs149738, rs171248, rs183574), Solute carrier family 15 member 2 (SLC15A2 rs2257212) in addition to genes involved in agiogenesis, like nitric oxide synthase 3 /endothelial NOS (NOS3/eNOS rs2070744, rs2070744, rs2070744, rs61722009, rs1799983), vascular endothelial growth factor A (VEGF-A rs25648, rs833061, rs699947, rs2010963), vascular endothelial growth factor C (VEGF-C rs4604006, rs664393), kinase insert domain receptor (KDR/VEGFR-2 rs2071559, rs2305948, rs1870377, rs4864950), hypoxia inducible factor 1 subunit alpha (HIF-1A rs1951795, rs10873142, rs12434438, rs12434438), fibroblast growth factor 2 (FGF2 rs308379, rs308447) were analyzed in this article. Some of these SNPs were associated with favora…
subject: Review Articles
  topic: section
subject: Liver cancer
  topic: keywords
subject: sorafenib
  topic: keywords
subject: genetic polymorphism
  topic: keywords
subject: treatment response
  topic: keywords
subject: adverse effects
  topic: keywords
creator: Saeed Khan
creator: Ayesha Akhtar
creator: Muhammad Hanif Bangash
rights: Copyright (c) 2024 Sagheer Ahmed https://creativecommons.org/licenses/by/4.0
date: 2024-12-30
publication date: 2024-12-30
starting page: 85
ending page: 114
doi: 10.55627/pmc.004.002.0555

Genetic Polymorphism in CYP3A4 and CYP3A5 Genes and their Association with the Clinical Response to Calcineurin Inhibitors; A Narrative Review
type: item
description: Calcineurin inhibitors, including cyclosporine and tacrolimus, are the fundamental pillars of immunosuppressant therapy in patients with allogeneic transplants. Calcineurin inhibitors are mainly the substrates for the enzymes CYP3A4 and CYP3A5. The literature search in this review has affirmed that many SNPs located in the genes responsible for CYP3A4 and CYP3A5 expression are associated with influencing the pharmacokinetics of calcineurin inhibitors and eventually maneuvering their efficacy and toxicity profiles. CYP3A5 A6986G (rs776746) had an association with the pharmacokinetics of cyclosporine and tacrolimus in transplant patients. The patients with the CYP3A5*3 (rs776746) allele had higher initial plasma concentrations of cyclosporine and tacrolimus, while those with the CYP3A5*1 (rs776746) allele had higher oral clearance of both drugs, resulting in lower initial plasma concentrations. More patient survival was also associated with the CYP3A5*1 genotype in the Caucasian population. Higher doses of cyclosporine were required in patients with allogeneic grafts carrying the CYP3A4*18B (rs28371759) allele in the Chinese population. In various other populations, it was revealed that therapeutic drug monitoring with calcineurin inhibitors was necessary in patients carrying the CYP3A4*1B (rs2740574) allele. CYP3A4*22 (rs35599367) carrying individuals were more prone to tacrolimus toxicity. CYP3A5A44G also affected the pharmacokinetics and efficacy of tacrolimus in Asian, white, and other populations. Many of these SNPs manifested no associations in numerous populations. Many confounding factors may have canceled out these associations. More studies are required to explore the effects of these SNPs on larger samples in order to validate these findings. Attempts should also be made to discover novel SNPs in these genes to find out more associations that can influence the overall clinical response to calcineurin inhibitors in transplant patients.
subject: Review Articles
  topic: section
subject: Calcineurin inhibitors
  topic: keywords
subject: cyclosporin
  topic: keywords
subject: tacrolimus
  topic: keywords
subject: CYP3A4
  topic: keywords
subject: CYP3A5
  topic: keywords
subject: allogeneic transplant
  topic: keywords
subject: genetic polymorphism
  topic: keywords
creator: Ahsan Ibrahim
rights: Copyright (c) 2024 Ahsan Ibrahim https://creativecommons.org/licenses/by/4.0
date: 2024-06-29
publication date: 2024-06-29
starting page: 21
ending page: 40
doi: 10.55627/pmc.004.001.0554

Editor's Summaries of the Articles Published in This Issue of Precision Medicine Communications
type: item
description: In this issue, Shah and colleagues reviewed and discussed the pharmacogenetics of tacrolimus in solid organ transplant patients, Ullah and colleagues performed a meta-analysis on the association of GABRG2 rs211037 gene polymorphism with epilepsies and pharmacoresistance to anti-epileptic drugs, Mansoor and colleagues carried out an integrative investigation for the prioritization of candidate genes and unveiled their interaction with celecoxib for targeted therapeutic applications, Nimra and Robab reviewed the pharmacogenomics of Leukemia for unlocking personalized treatment strategies, Hussain and colleagues investigated the association of GATM gene polymorphism with statin-induced myopathy.
subject: In This Issue
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 81
ending page: 82
doi: 10.55627/pmc.003.02.0486

Rapid & Low-Cost DPYD Genotyping to Guide Fluoropyrimidine Treatment in Cancer Patients
type: item
description: DPYD (dihydropyrimidine dehydrogenase) genotyping is relevant in the context of cancer treatment, particularly with fluoropyrimidine-based chemotherapy drugs such as 5-fluorouracil (5-FU) and capecitabine. Dihydropyrimidine dehydrogenase is an enzyme involved in the metabolism of these drugs, and certain genetic variants in the DPYD gene can lead to reduced enzyme activity, potentially causing severe and life-threatening toxicities. The implementation of upfront DPYD genotyping involves testing patients for specific DPYD variants before starting fluoropyrimidine-based chemotherapy. Pinheiro and colleagues assessed the frequency of the four most common and well-established DPYD variants associated with fluoropyrimidine toxicity and implemented a relatively low-cost and high-throughput genotyping assay for their detection. Their study comprised 457 patients that were genotyped for the DPYD c.1129-5923C>G, c.1679T>G, c.1905 + 1G>A and c.2846A>T variants, either by Sanger sequencing or kompetitive allele-specific PCR (KASP) technology. Of these, 172 patients presented toxicity during treatment with fluoropyrimidines (post-treatment group), and 285 were tested before treatment (pretreatment group). A little more than 7% of patients were DPYD homozygous. The most common variant they found was c.2846A>T. The KASP assays designed in this study presented 100% genotype concordance with the results obtained by Sanger sequencing. The authors concluded that the combined assessment of the four DPYD variants increases the identification of patients at high risk for developing fluoropyrimidine toxicity. They also found KASP genotyping a low-cost and rapid turnaround time assay. Pharmacogenet Genomics. 2023 Oct 1;33(8):165-171. doi: 10.1097/FPC.0000000000000505.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 83
ending page: 86
doi: 10.55627/pmc.003.02.0485

Pharmacogenomic Variants Affecting Statins Response in Sri Lanka
type: item
description: Pharmacogenomic variants can influence the efficacy and toxicity of statins, which are commonly prescribed medications for managing cholesterol levels and reducing the risk of cardiovascular events. Statins work by inhibiting HMG-CoA reductase, an enzyme involved in cholesterol synthesis. Ranasinghe and colleagues investigated the diversity of pharmacogenetic variants of statins among Sri Lankans. They compared the minor allele frequencies (MAFs) of 426 Sri Lankans with other populations. They observed the following MAFs in common genes usually associated with statins response and toxicity. The MAF of SLCO1B1*5 (rs4149056 [T>C]) was 18.19% (95% CI: 14.53-21.85), MAFs of CYP2C9*2 (rs1799853 [C>T]) and CYP2C9*3 (rs1057910 [A>C]) were 2.58% (95% CI: 1.08-4.08) and 10.30% (95% CI: 7.75-13.61), respectively, MAFs of rs2231142 (G>T) (ABCG2), rs7412 (C>T) (APOE) and rs20455 (A>G) (KIF6) variants were 10.68% (95% CI: 7.76-13.60), 3.52% (95% CI: 1.77-5.27) and 50.7% (95% CI: 45.96-55.45), respectively. They found the frequency of two variants higher in the Sri Lankan population compared to the Western and other Asian populations (rs20455 (A>G), CYP2C9*3 (A>C) and SLCO1B1*5 (T>C)). They concluded that genetic polymorphisms affecting efficacy of statins (KIF6 [rs20455], CYP2C9*3) and increased risk of statin-induced myotoxicity (SLCO1B1*5 and CYP2C9*3) were prevalent in higher frequencies among Sri Lankans compared with Western populations. Pharmacogenomics. 2023 Oct;24(15):809-819. doi: 10.2217/pgs-2023-0149.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 83
ending page: 86
doi: 10.55627/pmc.003.02.0484

Prediction of PEGylated INF-α Treatment Response in Hepatitis B Patients
type: item
description: Genetic polymorphisms can influence the response to antiviral therapy in patients with chronic hepatitis B (CHB). The variability in treatment response is multifactorial, and genetic factors play a role in how individuals metabolize and respond to antiviral medications. Wang and colleagues investigated the genetic association of the IL-6 rs1800796 polymorphism with PEGylated IFN-α (PegIFN-α) treatment response in hepatitis B surface antigen (HBsAg)-positive CHB patients. After sequencing the patients’ samples, they found that more patients with the combined response (n = 95) carried IL-6 rs1800796 GC genotypes, while CC genotype carriers possessed reduced HBeAg seroconversion rate and high values of hepatitis B virus DNA. They also found that PegIFN-α treatment response was also associated with the baseline HBsAg and HBeAg and IL-6 rs1800796 CC genotype. The authors concluded that PegIFN-α response may be predicted by detecting IL-6 rs1800796 genotype in CHB patients. Per Med. 2023 Nov;20(6):503-510. doi: 10.2217/pme-2023-0089.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 83
ending page: 86
doi: 10.55627/pmc.003.02.0483

TREX1 Mutations in Aicardi–Goutières Syndrome with Congenital Glaucoma
type: item
description: Aicardi–Goutières syndrome (AGS) is a rare genetic disorder that primarily affects the brain, the skin, and the immune system. It is characterized by a group of symptoms that mimic the effects of a viral infection, leading to inflammation in various tissues. Świerczyńska and colleagues presented a case of a neonate with hypotrophy, microcephaly, frostbite-like skin lesions, thrombocytopenia, elevated liver enzymes, and hepatosplenomegaly and showed that she had ‘three prime repair exonuclease 1’ (TREX1) gene mutations. The genetic investigation found pathogenic mutations, c.490C>T and c.222del (novel mutation) in the TREX1 gene showing AGS type 1 (AGS1). High serum IFN-α levels were also found. Later examination showed multiple ocular abnormalities including intraocular pressure (IOP) of 51 mmHg in the right eye and 49 in the left eye. The patient was diagnosed with congenital glaucoma, and it was managed with trabeculectomy with a basal iridectomy of both eyes, resulting in a reduction and stabilization in the IOP to 12 mmHg in the right eye and 10 mmHg in the left eye without any hypotensive eyedrops. This case report adds to the growing evidence of the involvement of the pathogenic c.490C>T and c.222del mutations in TREX1 in ophthalmic abnormalities. J Pers Med. 2023 Nov 15;13(11):1609. doi: 10.3390/jpm13111609.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 83
ending page: 86
doi: 10.55627/pmc.003.02.0482

Predictors of Voriconazole Concentration in Hematopoietic Stem Cell Transplant
type: item
description: The variability in individual response to voriconazole can be influenced by both genetic factors (pharmacogenetics) and clinical factors. Understanding the pharmacogenetic and clinical predictors of voriconazole response is important for optimizing its use and minimizing adverse effects. Patel and colleagues investigated the association of genetic polymorphisms in ABCB1, ABCG2, CYP2C9, CYP3A4, CYP3A5, and the CYP2C genes with voriconazole trough concentrations in patients receiving CYP2C19-guided dosing. They performed a retrospective study in allogeneic hematopoietic cell transplant patients receiving CYP2C19-guided voriconazole dosing. They found that 36% of 185 patients were subtherapeutic. They also found that CYP2C19, age, and letermovir use were associated with voriconazole concentrations. Variations in the ABCG2 gene were associated with voriconazole concentrations in patients receiving 200 mg dose. Genetic polymorphisms in CYP2C19 and letermovir use were associated with subtherapeutic status. They concluded that CYP2C19 phenotype and letermovir use were significantly associated with subtherapeutic voriconazole concentrations and may be used to improve voriconazole precision dosing. Pharmacogenomics J. 2023 Nov;23(6):201-209. doi: 10.1038/s41397-023-00320-z.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 83
ending page: 86
doi: 10.55627/pmc.003.02.0481

Role of Microbiome in Personalized Medicine
type: item
description: The human microbiome, which consists of trillions of microorganisms residing in and on the human body, plays a significant role in personalized medicine. The microbiome has been recognized as a critical factor influencing various aspects of health and disease, and its consideration in personalized medicine is expanding. Factors such as genetics, diet, environment, and lifestyle contribute to the unique microbial profile of each person. Therefore, the microbiome varies between individuals in terms of its composition and diversity. The microbiome can influence drug metabolism and response. Some drugs undergo biotransformation by gut bacteria, affecting the pharmacokinetics and efficacy of the drugs. Understanding an individual's microbiome may help predict and optimize drug responses. The microbiome also plays a crucial role in shaping the immune system. Imbalances or dysbiosis in the microbiome have been linked to various immune-related disorders. Considering the microbiome in the development of immunotherapies and treatments for autoimmune diseases would help in developing personalized medicine. The bidirectional communication between the gut and the brain, known as the gut-brain axis, is influenced by the microbiome. The gut microbiome may impact neurological conditions, mental health, and even responses to certain medications. Personalized approaches may consider the gut-brain axis in neurological and psychiatric disorders. Similarly, alterations in the microbiome have been associated with various diseases, including inflammatory bowel disease, obesity, diabetes, and cancer. An individual's unique microbiome is crucial when designing personalized dietary recommendations. The microbiome influences metabolism, nutrient absorption, and overall health. Microbial biomarkers are being explored for disease diagnosis, prognosis, and treatment response. The identification of specific microbial signatures associated with certain conditions may aid in personalized diagnostic…
subject: Editorial
  topic: section
creator: Sami Siraj
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 79
ending page: 79
doi: 10.55627/pmc.003.02.0480

Association of GABRG2 rs211037 Gene Polymorphism With Epilepsies and Pharmacoresistance to Anti-Epileptic Drugs; A Meta-Analysis
type: item
description: GABRG2 protein which is a crucial part of GABA receptor encoded by the gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene. The exonic GABRG2 rs211037 gene polymorphism has been commonly explore with respect to variable association to different types of epilepsies (all types, IGE and FS) and AEDs response. The current meta-analysis study was designed to explore whether the GABARG2 C588 T (rs211037) genetic variant predicts susceptibility to different types epilepsy and pharmacoresistance to AEDs. Twenty studies were included, contained 3351 epileptic patients and 3649 controls in meta-analysis, for the association GABRG2 rs211037 polymorphism with susceptibility to different types of epilepsy. Similarly, five studies comprised of 632 responder patients and 401 non-responder patients in meta-analysis, were selected for the evaluation of the GABRG2 rs211037 polymorphism to pharmacoresistance to AEDs. Meta-analysis was performed separately for FS and IGE in Asian and Caucasian population for association to epilepsies and pharmacoresistance to AEDs but pharmacoresistance to AEDs in FS and IGE was not performed in Asian and Caucasian due to limited number of studies. Meta-analysis showed a significant link between GABRG2 rs211037 polymorphism and susceptibility to all types of epilepsies in total Population in (CC vs CT, OR 1.03, 95% CI 0.0–1.2, p = 0.0006 and CC vs TT, OR 0.03, 95% CI 0.8–1.2, p = 0.01) genetic models. Similarly, a significant association of this polymorphisms with all types of epilepsy was found with Asian population in genetic models of CC vs CT( OR 0.86 (0.7-1.0,p=0.11), CC vs TT (OR 0.67 (0.5-0.9, p=0.000), but CC vs CT+TT genetic model shows the association of all types of epilepsies in Asian as well Caucasian population ( OR 0.6 (0.5-0.7), p=0.001 and OR 1.05 (0.9-1.2), p=0.000). Similarly, CC vs CT, CC vs TT and CC vs CT+TT genetic models were also associated with IGE and FS epilepsies in total population, Asian and Caucasian population. Th…
subject: Meta-Analysis
  topic: section
creator: Shakir Ullah
creator: Saad Ali
creator: Nisar Ahmad
creator: Muhammad Zakria
creator: Muhammad Nabi
creator: Muhammad Ikram
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 119
ending page: 132
doi: 10.55627/pmc.003.02.0450

Integrative Investigation and Prioritization of Candidate Genes PTGS-2 and VEGF: Unveiling their Interaction with Celecoxib for Targeted Therapeutic Applications
type: item
description: There is a huge amount of data available on genes interacting with celecoxib in terms of drug response; however, these studies are inconsistent. To overcome this inconsistency, there is a dire need to integrate the available data and categorize genes interacting with celecoxib. We conducted the extraction of data from published articles (n=30511) with reference to celecoxib-gene interactions from online literature sources using semi-automated text mining approach. Scoring algorithms were developed by assigning every gene a score depending on the available evidence according to Coriell Personalized Medicine Collaborative Pharmacogenomics Appraisal evidence scoring systems. We generated prioritized gene sets based on evidence scores. Twenty-seven genes with evidence were identified to be associated with the response of celecoxib from the literature search. Seven genes were found to affect clinical outcomes of celecoxib, whereas, thirteen genes were found associated with pharmacodynamics and pharmacokinetics and seven genes were identified with potential clinical relevance. Our analysis specified that celecoxib responds better in an individual with increased expression of PTGS-2 and VEGF genes. Thus, we utilized a semi-automated machine learning approach to extract genes from a wide-ranging corpus of scientific literature and prioritized a set of twenty-seven genes based on the consistency and strength of evidence. Furthermore, these identified genes can be used for validation and or replication in multiethnic cohorts and animal models to evaluate the response variation of celecoxib.
subject: Research Articles
  topic: section
subject: Genetic polymorphism
  topic: keywords
subject: PTGS-2
  topic: keywords
subject: VEGF
  topic: keywords
subject: celecoxib
  topic: keywords
subject: gene-drug interaction
  topic: keywords
subject: genome-wide association studies
  topic: keywords
creator: Momna Mansoor
creator: Nabi Shah
creator: Anum
creator: Muhammad Imran Amirzada
creator: Zia Uddin
creator: Muhammad Ikram
creator: Abdul Jabbar Shah
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 87
ending page: 103
doi: 10.55627/pmc.003.02.0446

Investigation of the Association of GATM Gene Polymorphisms with Statin-Induced Myopathy
type: item
description: Statins are one of the mainstay medicines for treating hyperlipidemia. The effect of statins can extend beyond their direct role in cholesterol transport to anti-inflammatory and plaque stabilization in coronary artery disease (CAD). Statins are known to reduce low-density lipoproteins (LDL) by up to 55%, which can inadvertently reduce the risk of cardiac events in patients. Strong clinical profile notwithstanding, statins are notorious for their muscle-related adverse effects. Some variations in genes such as glycine amidinotransferase (GATM) have been implicated in this side effect; however, the reports are not all congruent. In the current study, a prospective cohort design was used to establish both drug efficacy and the incidence of muscle-rated adverse reactions in patients receiving atorvastatin and rosuvastatin. The muscle adverse effects were recorded using the “Statin Associated Muscle Symptoms-Clinical Index” (SAMS-CI) tool. Drug plasma levels were recorded using LC-MS, and GATM rs9806699 was genotype using direct Sanger sequencing. A binary logistic model was used to determine the association between genotypes and the incidence of muscle symptoms, whereas stepwise linear regression was used to determine the association between plasma concentration, genetics, and muscle symptoms. Among 130 enrolled patients, 97(74.62%) received rosuvastatin 10 mg (once daily), and 33 (25.38%) received atorvastatin 20 mg (once daily). A total of 26 patients reported adverse drug reactions according to the SAMS-CI. The genotype frequency of GATM rs9806699-GG was 45.74%, whereas the heterozygous genotype (AG) was 34(36.17%), and the AA genotype was 18.09%. There was no significant difference found between the plasma concentrations of both rosuvastatin and atorvastatin among GATM rs9806699 genotypes. Despite the high incidence of muscular adverse effects, there was no significant association between GATM genotypes and SAMS.
subject: Research Articles
  topic: section
subject: Atorvastatin
  topic: keywords
subject: Rosuvastatin
  topic: keywords
subject: Glycine amidinotransferase gene
  topic: keywords
subject: Single nucleotide polymorphism
  topic: keywords
subject: Statin-induced myopathy
  topic: keywords
creator: Arif Hussain
creator: Muhammad Zakria
creator: Shafiq Ahmed Tariq
creator: Muhammad Abdul Rauf
creator: Jamil Ahmad
creator: Muhammad Fawad Rasool
creator: Iftikhar Ali
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 105
ending page: 118
doi: 10.55627/pmc.003.02.0430

Pharmacogenomics of Leukemia; Unlocking Personalized Treatment Strategies
type: item
description: Leukemia, a diverse group of blood cancers, continues to present significant challenges in diagnosis and treatment. Recent advancements in pharmacogenomics have opened new avenues for tailoring therapeutic strategies to individual patients' unique genetic and molecular characteristics. In leukemia, genetic polymorphisms have been identified that influence drug metabolism, efficacy, and the risk of adverse effects. Notable examples include TPMT variants affecting thiopurine treatment in acute lymphoblastic leukemia (ALL), UGT1A1 polymorphisms impacting irinotecan toxicity in acute myeloid leukemia (AML), and SLCO1B1 variants influencing methotrexate response in ALL. Targeted therapies have revolutionized leukemia treatment, focusing on specific genetic abnormalities. Tyrosine kinase inhibitors (TKIs) like imatinib have successfully treated chronic myeloid leukemia (CML) with the BCR-ABL fusion gene. Similarly, immunotherapies, such as CAR T-cell therapy, reshape treatment paradigms for B-cell ALL. The personalized approach minimizes adverse effects while optimizing treatment efficacy. Moreover, genetic markers are aiding in identifying patients at higher risk of developing cardiotoxicity from anthracycline chemotherapy. This article provides an overview of the evolving landscape of pharmacogenomics in leukemia, highlighting key findings and trends. Combinatorial therapies, biomarker discovery, and patient-centric care are expected to enhance outcomes and survivorship.
subject: Review Articles
  topic: section
subject: Acute lymphoblastic leukemia
  topic: keywords
subject: immunotherapies
  topic: keywords
subject: genetic polymorphism
  topic: keywords
subject: pharmacogenomics
  topic: keywords
subject: adverse effects
  topic: keywords
subject: efficacy
  topic: keywords
creator: Mehak Nimra
creator: Sana Robab
creator: Muhammad Fawad Rasool
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 151
ending page: 160
doi: 10.55627/pmc.003.02.0388

Pharmacogenetics of Tacrolimus in Solid Organ Transplant Patients
type: item
description: Tacrolimus is one of the most important immunosuppressant drugs used in organ transplants. The primary enzymes responsible for the metabolism of tacrolimus are cytochrome P450 3A4 and CYP3A5. Single nucleotide polymorphisms (SNPs) in the CYP3A4, CYP3A5, and ABCB1 genes, in particular, have been connected to changes in tacrolimus metabolism and clearance. Tacrolimus has a narrow therapeutic index and dose monitoring and adjustment are required. Pharmacogenetic analyses have demonstrated that CYP3A5 genotypes account for a substantial amount of the variation in tacrolimus metabolism and clearance. Tacrolimus pharmacokinetics have also been widely studied in relation to ABCB1 polymorphisms, and some studies have demonstrated a notable impact on tacrolimus hepatic concentrations. Contradictory findings, however, have been documented, highlighting the necessity for more research in this field. In this manuscript, we compiled, reviewed, and discussed pharmacogenetic studies showing associations of genetic polymorphism with the efficacy and/or adverse effects of tacrolimus in solid organ transplant patients. We argue that knowledge of the function of genetic markers—specifically, SNPs in the CYP3A4, CYP3A5, and ABCB1 genes—is essential to maximizing the use of tacrolimus in clinical settings. This knowledge makes it possible to create customized treatment plans that will improve tacrolimus's effectiveness and safety for organ transplant recipients. Tacrolimus medication tailored to each patient based on genetic markers presents a viable way to enhance outcomes for organ transplant recipients. We recommend that tacrolimus dosage be customized to each patient's distinct genetic profile by identifying particular SNPs in the CYP3A4, CYP3A5, and ABCB1 genes. By doing this, the danger of side effects can be reduced and the drug's effectiveness can be maximized.
subject: Review Articles
  topic: section
subject: Solid organ transplant
  topic: keywords
subject: tacrolimus
  topic: keywords
subject: single nucleotide polymorphism
  topic: keywords
subject: genetic variation
  topic: keywords
subject: adverse effects
  topic: keywords
subject: efficacy
  topic: keywords
creator: Furqan Ali Shah
creator: Amanat Ali
creator: Zarafshan Bader
creator: Gul Hassan
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-12-31
publication date: 2023-12-31
starting page: 133
ending page: 150
doi: 10.55627/pmc.003.02.0387

Editor's Summaries of the Articles Published in This Issue of Precision Medicine Communications
type: item
description: In this issue, Rafiq et al, investigated noncancerous FDA-approved drugs for repurposing through molecular docking studies in Breast Cancer patients after their target cystic fibrosis transmembrane conductance regulator protein (CFTR) detection in breast cancer patients. Konain and colleagues evaluate the anticancer potential of commonly used angiotensin receptor blocker (ARB) telmisartan and validate it through molecular techniques, Bangash and friends investigate whether the efficacy and adverse effects of fluvoxamine are associated with polymorphism in the CYP2D6 gene in patients with depression; Mubarak and colleagues reviewed studies aimed at investigating resistance to Carbamazepine in epilepsy patients influenced by the polymorphism of genes encoding metabolic enzymes and drug transporters, while Riaz and Chen provide general information about Type 2diabetes mellitus, treatment challenges, and pharmacogenetic aspects of metformin pharmacotherapy in type 2 diabetes mellitus.
subject: In This Issue
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-06-30
publication date: 2023-06-30
starting page: 03
ending page: 04
doi: 10.55627/pmc.003.01.0349

Impact of CYP3A5 Genotype on De-novo LCP Tacrolimus Dosing in Kidney Transplantation
type: item
description: The CYP3A5 gene encodes an enzyme called cytochrome P450 3A5, which is involved in the metabolism of many drugs, including tacrolimus. Tacrolimus is an immunosuppressive medication commonly used in kidney transplantation to prevent organ rejection. The CYP3A5 genotype can influence the metabolism and clearance of tacrolimus, leading to variations in the drug levels and response. LCP tac (an extended-release form of tacrolimus) has a recommended starting dose of 0.14 mg/kg/day in kidney transplants. Rao et al assessed the influence of CYP3A5 genotypes on perioperative LCP tac dosing and monitoring in adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured, and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele). They concluded that CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers. Pharmacogenet Genomics. 2023 Apr 1;33(3):59-65. doi: 10.1097/FPC.0000000000000494.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-06-30
publication date: 2023-06-30
starting page: 05
ending page: 09
doi: 10.55627/pmc.003.01.0318

Genetic Polymorphism & Methotrexate Therapy Outcomes in Rheumatoid Arthritis
type: item
description: Methotrexate (MTX) is commonly used as a disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms in key enzymes involved in MTX metabolism, such as methyl tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have been studied for their potential impact on MTX therapy outcomes in early RA patients. Zhang et al investigated a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) was enrolled, and all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and Sanger sequencing to verify its accuracy. The distribution of the three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoking (OR = 0.088, P = 0.037), drinking alcohol (OR = 0.039, P = 0.016), and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution, and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups. Their findings suggest that the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response. Pharmgenomics Pers Med. 2023 May 2;16:407-423. doi: 10.2147/PGPM.S404949. eCollection 2023.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-06-30
publication date: 2023-06-30
starting page: 05
ending page: 09
doi: 10.55627/pmc.003.01.0317

Genetic Variation in OPRK1 Gene and Opioid Use Disorder
type: item
description: The OPRK gene encodes the kappa opioid receptor, which is involved in modulating the effects of opioids in the brain. Polymorphisms in the OPRK1 gene have been investigated for their potential association with opioid use disorder (OUD) and related phenotypes. OUD refers to a problematic pattern of opioid use characterized by a loss of control over use, craving, and negative consequences. To evaluate the association between OPRK1 rs963549 and rs997917 and opioid use disorder (OUD) and related phenotypes, Özkan-Kotiloğlu et al conducted a study. A sample of 208 individuals with (n = 100) and without (n = 108) OUD were enrolled. OPRK1 rs963549 and rs997917 were analyzed by PCR-RFLP. Craving, opioid withdrawal, and the intensity of depressive and anxiety symptoms were measured by the appropriate scales. OPRK1 rs963549 variation showed a trend of association with decreased opioid withdrawal. No significant associations were found between OPRK1 rs963549 and rs997917 polymorphisms and craving, depression or anxiety symptoms. Neither single OPRK1 SNPs nor OPRK1 haplotypes were associated with OUD. Their results could be useful for treatment failures of individuals who experience greater opioid withdrawal due to their OPRK1 rs963549 genotypes. Pharmacogenomics. 2023 May 11. doi: 10.2217/pgs-2023-0037. Online ahead of print.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-06-30
publication date: 2023-06-30
starting page: 05
ending page: 09
doi: 10.55627/pmc.003.01.0316

Side Effects and Genetic Variation During Depression in Taiwanese Han Population
type: item
description: Genetic variation can play a role in individual differences in the response to medications used for the treatment of depression, as well as in the occurrence of side effects. While there have been studies investigating genetic factors associated with antidepressant response and side effects, it is important to note that the field of pharmacogenetics is complex and influenced by multiple genetic and environmental factors. In the case of the Taiwanese Han population and depression, limited specific studies examining the relationship between genetic variation and antidepressant response or side effects have been conducted. Huang and colleagues analyzed the syndromal factor structures of the Hamilton Depression Rating Scale in 479 patients with MDD by using exploratory factor analysis. All patients were followed up biweekly for 8 weeks. In total, 33 independent SNPs for treatment responses were tested in a mixed model, 12 of which demonstrated a p value <0.05. The most significant SNP was rs2182717 in the ENSR00000803469 gene located on chromosome 6 for the core syndromal factor (β = -0.638, p = 1.8 × 10-4) in terms of symptom improvement over time. Patients with a GG or GA genotype with the rs2182717 SNP also exhibited a treatment response (β = 0.089, p = 2.0 × 10-6) at week 4. Moreover, rs1836075352 was associated with sexual side effects (p = 3.2 × 10-8). Pathway and network analyses using the identified SNPs revealed potential biological functions involved in treatment response, such as neurodevelopment-related functions and immune processes. In conclusion, they identified loci that may affect the clinical response to treatment with antidepressants in the context of empirically defined depressive syndromal factors and side effects among the Taiwanese Han population, thus providing novel biological targets for further investigation. Pharmacogenomics J. 2023 May;23(2-3):50-59. doi: 10.1038/s41397-023-00298-8.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-06-30
publication date: 2023-06-30
starting page: 05
ending page: 09
doi: 10.55627/pmc.003.01.0315

Pregnane X Receptor Gene Variation and Total Mortality in Nonalcoholic Fatty Liver Disease
type: item
description: The pregnane X receptor (PXR) is a nuclear receptor that plays a role in regulating the metabolism and clearance of drugs and xenobiotics in the liver. Variations in the PXR gene, including the rs7643645 variant, have been associated with altered PXR activity and potential implications for various liver-related conditions, including nonalcoholic fatty liver disease (NAFLD). It is known that the more progressive the NAFLD, the higher the hepatic and extra-hepatic mortality and morbidity. Käräjämäki et al investigated the total mortality in Finnish middle-aged ultrasonographically verified NAFLD patients with PXR rs7643645 variants. In up to 30 years of follow-up, PXR rs7643645 GG subjects were at an increased risk of total mortality compared with AA/AG subjects. The statistically significant difference prevailed after multiple adjustments for potentially confounding factors, RR, 2.024 (1.191-3.440), P = 0.009. In the subjects without NAFLD, the mortality risk was not associated with rs7643645 variants, 1.051 (0.708-1.560; P = 0.804). As the rs7643645 G variant disrupts a putative hepatocyte nuclear factor 4α binding site located in the PXR gene promoter and is associated with lower hepatic expression of PXR and its target genes, their result suggests that genetic disruption of xenobiotic metabolism increases mortality in subjects with NAFLD. Pharmacogenet Genomics. 2023 Feb 1;33(2):35-39. doi: 10.1097/FPC.0000000000000489.
subject: Editor's Choice
  topic: section
creator: Editorial Staff
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-06-30
publication date: 2023-06-30
starting page: 05
ending page: 09
doi: 10.55627/pmc.003.01.0314

Precision Medicine Approaches for Psychosis Treatment
type: item
description: Precision The precision medicine approach takes into account individual variability in genes, environment, and lifestyle and holds great promise in revolutionizing the treatment of various disorders, including psychosis. Psychosis is a mental health condition characterized by a loss of contact with reality, and it can occur in disorders such as schizophrenia and bipolar disorder. By integrating psychiatry and neurology, precision medicine aims to provide personalized and targeted interventions for individuals with psychosis. Several approaches are used for improved treatment outcomes in psychosis patients. Genetic biomarkers: Advances in genomic research have identified genetic variations associated with an increased risk of developing psychosis. Understanding these genetic biomarkers can help identify individuals at risk early and tailor treatment strategies based on their genetic profile. Genetic testing can assist in determining the optimal medication selection, dosage, and potential side effects. Pharmacogenomics: Psychiatric medications, including antipsychotics, can have varying efficacy and side effect profiles among different individuals. Pharmacogenomics studies the influence of genetic variations on drug response, metabolism, and side effects. By analyzing an individual's genetic makeup, clinicians can predict their response to specific medications and adjust treatment plans accordingly, improving treatment outcomes and reducing adverse effects. Neuroimaging and biomarkers: Neuroimaging techniques, such as magnetic resonance imaging (MRI) and functional MRI (fMRI), can provide insights into brain structure, function, and connectivity. These imaging methods, combined with other biomarkers like blood-based markers or cerebrospinal fluid analysis, can help identify subtypes within the broad category of psychosis. These subtypes can inform treatment selection and predict treatment response, leading to more targeted interventions. Digital phenotyping and wearab…
subject: Editorial
  topic: section
creator: Sami Siraj
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-07-17
publication date: 2023-07-17
starting page: 01
ending page: 02
doi: 10.55627/pmc.003.01.0313

Exploring the Potential of Drug Repurposing: Detection of Cystic Fibrosis Transmembrane Conductance Regulator as a Biomarker in Breast Cancer Patients
type: item
description: Despite the advancements in cancer treatment and the benefits of personalized medicine, breast cancer (BC) remains a significant health concern. Moreover, conventional treatment options are costly and often associated with severe side effects, highlighting the need to identify new biomarkers and innovative treatment strategies for BC. Drug repurposing presents an approach that expands the therapeutic window further to mitigate the financial burden and minimize the potential harm caused by existing anticancer drugs. In the present study, we aim to suggest noncancerous FDA-approved drugs for repurposing, through molecular docking studies in BC, after their target cystic fibrosis transmembrane conductance regulator protein (CFTR) detection in BC. We used a drug repurposing approach to identify the target protein CFTR and drugs that target CFTR. MOE (molecular operating environment) was used to analyze the interaction between CFTR and its targeting drugs. For experimental work, we did Immunofluorescence staining on BC tissue. We found that glyburide and tezacaftor were the top antagonist and agonists, respectively. We detected CFTR expression in all ten samples except Triple-Negative Breast Cancer (TNBC). CFTR and estrogen receptor alpha co-expressed at 6.78%, suggesting a potential relationship. High-grade tumors showed CFTR expression below 8%, indicating CFTR down-regulation and its role in tumor aggressiveness. Our study is a preliminary step towards in-vitro and in-vivo experiments on repurposing CFTR-targeting drugs in BC. Glyburide may inhibit CFTR's estrogen production, while tezacaftor can enhance CFTR action to overcome tumor aggressiveness.
subject: Research Articles
  topic: section
subject: Breast cancer
  topic: keywords
subject: new biomarker
  topic: keywords
subject: drug repurposing
  topic: keywords
subject: CFTR
  topic: keywords
subject: glyburide
  topic: keywords
subject: tezacaftor
  topic: keywords
creator: Sobia Rafiq
creator: Sana Khan
creator: Shumaila Wazir
creator: Haseena Nawaz
creator: Mah Muneer Khan
creator: Sadia Fatima
creator: Babar Jamal
creator: Asif Ali
creator: Ishaq N Khan
rights: Copyright (c) 2023 Precision Medicine Communications https://creativecommons.org/licenses/by/4.0
date: 2023-06-30
publication date: 2023-06-30
starting page: 11
ending page: 26
doi: 10.55627/pmc.003.01.0300