تأثير تعدد الاشكال الجينية (COQ2) على حدوث الاعتلال العضلي لدى المرضى المعالجين بالاتورفستاتين في محافظة كربلاء

Effect of COQ2 Gene Polymorphism on incidence of myopathy in patients treated with atorvastatin in Kerbala Province

Abstract

Background: The COQ2 gene 4-hydroxybenzoate encoding polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to statin induce myopathy. Myopathy is a major side effect of statins that leads to statin intolerance and discontinuation.
Aims of study: The aim of this study is to detect the role of genetic polymorphism of COQ2 gene particularly COQ2 (A>G) (rs6535454) and COQ2 (C>A) (rs6818847) that involved in the incidence of myopathy in Iraqi patients treated with 40mg atorvastatin.
Patients and methods: This cross-sectional observational study was done at Imam Al-Hussein Medical City in Kerbala. One hundred fifty patients with atorvastatin drug were selected to participate in this study. All patients enrolled in this study with age ranged (30-65) were treated with atorvastatin tablet (40mg) once daily. Blood samples were obtained from patients who had signed informed consent for genetic testing and it was used for measurement of Coenzyme Q10. lipid profile (cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein), renal function test (creatinine), creatine kinase, and thyroid stimulating hormone. This study used Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS PCR) for detection of COQ2 (A>G) (rs6535454) and COQ2 (C>A) (rs6818847).

Results: The obtained results from this study have detected multiple genotypes of COQ2 gene particularly COQ2 (A>G) (rs6535454) and COQ2 (C>A) (rs6818847), that include the homozygous wild genotype (AA), homozygous mutant (GG) and heterozygous (AG) genotype of COQ2 (A>G) (rs6535454) while for COQ2 (C>A) (rs6818847) that include the homozygous wild genotype (CC), homozygous mutant (AA) and heterozygous (CA) genotype detected in statin taking patients participated in this study. Regarding to the level of coenzyme Q10 and creatine kinase in the serum, the present study showed that significant association (p>0.05) between the studied SNPS of COQ2 gene and serum CoQ10 level, while non significant association (p>0.05) between the studied SNPs of COQ2 gene and serum creatine kinase level in the statin taking patients included in the study. Conclusion: In the Iraqi dyslipidemic patients treated with high dose of atorvastatin, there is a significant effect of common polymorphisms (rs6535454 and rs6818847) within the COQ2 gene, this poses a risk of developing myopathy associated with the use of atorvastatin