What question did this study set out to answer?

To identify genetic variants associated with the development of statin-induced myopathy in patients receiving high-dose simvastatin.

July 23, 2008New England Journal of MedicineOpen Access

SLCO1B1 Variants and Statin-Induced Myopathy — A Genomewide Study

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Overview

Randomized trial uncovers a strong link between SLCO1B1 gene variants and myopathy in simvastatin-treated individuals, indicating that genetic testing can improve statin safety.

Key Points

To identify genetic variants associated with the development of statin-induced myopathy in patients receiving high-dose simvastatin.
Conducted a genome-wide association study using ~300,000 markers in 85 subjects with definite or incipient myopathy and 90 controls receiving 80 mg daily simvastatin within a 12,000-participant trial (ISRCTN74348595).
Replicated candidate variant associations in an independent clinical trial cohort of 20,000 participants receiving 40 mg of simvastatin daily.
Genome-wide scanning identified a single strong association between myopathy and the rs4363657 SNP in the SLCO1B1 gene (P=4x10^-9), which was in near-complete linkage disequilibrium (r^2=0.97) with the nonsynonymous rs4149056 SNP.
The rs4149056 C allele exhibited an odds ratio for myopathy of 4.5 (95% CI, 2.6 to 7.7) per copy and 16.9 (95% CI, 4.7 to 61.1) in CC versus TT homozygotes, accounting for over 60% of myopathy cases.
Replication in the trial of 40 mg daily simvastatin confirmed the association of rs4149056 with myopathy and revealed an association with the cholesterol-lowering efficacy of simvastatin.

Cite This Study

A 2008 study studied this question.

synapsesocial.com/papers/6a7c9374076dbfca02ba5b8a https://doi.org/10.1056/nejmoa0801936

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July 23, 2008New England Journal of MedicineOpen Access

SLCO1B1 Variants and Statin-Induced Myopathy — A Genomewide Study

View Full Paper

Ask AI

Bookmark

Discussion

Member takes

Overview

Randomized trial uncovers a strong link between SLCO1B1 gene variants and myopathy in simvastatin-treated individuals, indicating that genetic testing can improve statin safety.

Key Points

To identify genetic variants associated with the development of statin-induced myopathy in patients receiving high-dose simvastatin.
Conducted a genome-wide association study using ~300,000 markers in 85 subjects with definite or incipient myopathy and 90 controls receiving 80 mg daily simvastatin within a 12,000-participant trial (ISRCTN74348595).
Replicated candidate variant associations in an independent clinical trial cohort of 20,000 participants receiving 40 mg of simvastatin daily.
Genome-wide scanning identified a single strong association between myopathy and the rs4363657 SNP in the SLCO1B1 gene (P=4x10^-9), which was in near-complete linkage disequilibrium (r^2=0.97) with the nonsynonymous rs4149056 SNP.
The rs4149056 C allele exhibited an odds ratio for myopathy of 4.5 (95% CI, 2.6 to 7.7) per copy and 16.9 (95% CI, 4.7 to 61.1) in CC versus TT homozygotes, accounting for over 60% of myopathy cases.
Replication in the trial of 40 mg daily simvastatin confirmed the association of rs4149056 with myopathy and revealed an association with the cholesterol-lowering efficacy of simvastatin.

Cite This Study

A 2008 study studied this question.

synapsesocial.com/papers/6a7c9374076dbfca02ba5b8a https://doi.org/10.1056/nejmoa0801936

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