Investigation of the Association of GATM Gene Polymorphisms with Statin-Induced Myopathy

Abstract

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.