دور تعدد الاشكال الجيني ( GATM) في حدوث الاعتلال العضلي لدى عينة من المرضى العراقيين المعالجين بالأتورفاستاتين في محافظة كربلاء

Role of GATM Gene Polymorphism in the Incidence of Myopathy in a Sample of 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 relationship between GATM gene polymorphism rs9806699 G > A, C, T and statin-related myopathy (SRM) in patients taking atorvastatin 40 mg.
Patients and methods: Cross sectional study with a total of 150 participants, both male and female, ranging in age from 28 to 65 years old and receiving daily oral doses of 40 mg of atorvastatin as monotherapy for hyperlipidemia for at least one month were involved in the study. Biochemical tests were performed on each participant to determine their lipid profile (total cholesterol, triglycerides, low density lipoprotein and high-density lipoprotein), serum creatinine, creatine kinase (C.K) and thyroid stimulating hormone levels. 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 homo 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: According to the results of the currents study, the GATM gene polymorphism rs9806699 G > A, C, T is not associated with statin-related myopathy but 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.