Association between variants of COQ2 and TNF-α genes and statin-induced toxicities in Bangladeshi hyperlipidemic patients

Abstract

Statin-induced toxicities are widely prevalent in Bangladesh, and most commonly include skeletal muscle disorders, which range from mild myalgia and myositis to rhabdomyolysis and myoglobinuria, and decreased libido. However, the genetic basis of statin-related toxicities is largely unknown in Bangladesh. As mutations in the coenzyme Q2 (COQ2) gene are associated with a severe type of myopathy and variations in the tumor necrosis factor (TNF)-α gene are related to serious inflammatory pain, in this study, we hypothesized that polymorphisms in COQ2 (rs4693075) and TNF-α (rs1799724) genes would be related to individual variation in statin intolerance. The most widespread cases of statin intolerance in Bangladesh (i.e., myopathy, myalgia, and decreased libido) were the chosen toxicities for this study. We studied 57 patients who developed different types of toxicities upon statin monotherapy and 94 matched controls who tolerated statins without any incident or complaint. In comparison with TNF-α polymorphisms, COQ2 genotypes showed significant associations with statin intolerance in patients with myopathy and decreased libido. For the mutant homozygous CC genotype, the odds ratio (OR) for myopathy was 10.10 (95% CI 2.60–39.23; p = 0.001), whereas for decreased libido, the OR was 0.18 (95% CI 0.03–0.97; p = 0.046). In conclusion, this preliminary pharmacogenetic study identifies that COQ2 gene polymorphism (rs4693075, G > C), not TNF-α gene polymorphism (rs1799724, C > T), is involved in causing statin-induced myopathy in Bangladeshi hyperlipidemic patients.