Effect of GATM Gene Polymorphism in the Incidence of Myopathy Among Iraqi Patients Treated with Atorvastatin in Kerbala Province

Abstract

Background: Statins are a class of drugs that block the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase, preventing de novo cholesterol synthesis. They are the most commonly prescribed lipid-lowering drugs in the world for the primary and secondary prevention of cardiovascular disease. Statin-associated muscular symptoms are the most common side effects of statin therapy, forcing patients to discontinue their medication. The Glycine amidinotransferase (GATM) gene codes for the mitochondrial enzyme L-arginine: glycine-amidinotransferase, a rate-limiting enzyme in creatine biosynthesis. Creatine is then necessary for normal muscle function. Statins have been shown to reduce GATM expression and thus creatine content in muscles, which may contribute to statin myopathy Aim of study: To investigate the relation between GATM gene polymorphism rs9806699 G > A, C, T and statin-related myopathy (SRM) in patients taking atorvastatin 40 mg. Patients and methods: One hundred fifty Iraqi male and female patients aged 28 to 65 years who were taking atorvastatin 40 mg once daily were chosen to participate in this cross-sectional study. Thyroid stimulating hormone and creatinine kinase were measured. The allele specific polymerase chain reaction technique was used to detect the rs9806699 G > A, C, T single nucleotide polymorphism (SNP). Results: The genotypes distribution of rs9806699 G > A, C, T was 20 (13.3%), 57 (38.0%) and 73 (48.7%) for homozygous wild (GG), heterozygous (GA), and homozygous mutant (AA) respectively, with no allele frequency for C and T. Despite a significant increase in mean creatine kinase in homozygous mutant (AA) patients compared to wild-type (GG) or heterozygous (GA) patients, there was no significant association between statin-related myopathy and GATM gene rs9806699 polymorphism. Conclusion: Although the rs9806699 SNP of the GATM gene is not associated with statin-related myopathy, it cannot be ruled out as one of the factors that contribute to myopathy since we observed that the A allele was found in more SRM patients than the G allele, with a significant increase in the mean creatine kinase level.