Abstract

BACKGROUND: Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study.

MATERIAL AND METHODS: SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment.

RESULTS: Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis.

CONCLUSIONS: In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.

Keywords: Atorvastatin Calcium - therapeutic use, Czech Republic - epidemiology, Diabetes Mellitus - epidemiology, Dose-Response Relationship, Drug, Dyslipidemias - genetics, Gene Frequency, Genetic Predisposition to Disease, Genotype, Hepatocytes - metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use, Models, Genetic, Muscular Diseases - genetics, Myalgia - genetics, Obesity - epidemiology, Organic Anion Transporters - physiology, Polymorphism, Single Nucleotide, Simvastatin - therapeutic use, Smoking - epidemiology