Journal Article

SLCO1B1 Variants and Statin-Induced Myopathy — A Genomewide Study

Gut, I, Link, E, Heath, S, Collins, R, Armitage, J, Lathrop, M, Matsuda, F, Parish, S, Bowman, L

2008

Overview

A genomewide screen of patients with myopathy who were taking high-dose simvastatin (80 mg per day) showed a strong association between myopathy and variants of SLCO1B1, which encodes an organic anion–transporting polypeptide. Approximately 60% of the cases of myopathy could be attributed to these variants. The association was replicated in an independent study. Genotyping SLCO1B1 variants may be helpful for tailoring the dosage of statins and safety monitoring. A genomewide screen of patients with myopathy who were taking high-dose simvastatin showed a strong association between myopathy and variants of SLCO1B1, which encodes an organic anion–transporting polypeptide. Evidence from large-scale, randomized studies shows that statin therapy reduces the incidence of heart attacks, strokes, and revascularization procedures by about one fifth for each reduction of 40 mg per deciliter (1 mmol per liter) in the low-density lipoprotein (LDL) cholesterol level. 1 In rare cases, statins can cause muscle pain or weakness in association with elevated creatine kinase levels (i.e., myopathy), and occasionally, this leads to muscle breakdown and myoglobin release (i.e., rhabdomyolysis), with a risk of renal failure and death. 2 The mechanisms by which statins cause myopathy remain unknown but appear to be related to statin concentrations in the . . .

• Publisher: Massachusetts Medical Society
• Subject: adverse effects / Aged / Arterial Occlusive Diseases / Arterial Occlusive Diseases - drug therapy / Biological and medical sciences / chemically induced / Cholesterol / Chromosomes / Chromosomes, Human, Pair 12 / Diabetes Mellitus / Diabetes Mellitus - drug therapy / Drug dosages / Drug therapy / Female / General aspects / Genetic Markers / genetics / Genotype / Human / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors / Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Kinases / Liver-Specific Organic Anion Transporter 1 / Male / Medical and Health Sciences / Medical sciences / Medicin och hälsovetenskap / Middle Aged / Muscular Diseases / Muscular Diseases - chemically induced / Muscular Diseases - genetics / Myocardial Infarction / Myocardial Infarction - drug therapy / Myocardial Infarction - prevention & control / Organic Anion Transporters / Organic Anion Transporters - genetics / Pair 12 / pharmacokinetics / Polymorphism / Polymorphism, Single Nucleotide / prevention & control / Risk / Simvastatin / Simvastatin - adverse effects / Simvastatin - therapeutic use / Single Nucleotide / Statins / therapeutic use