Genetic determinants of statin intolerance

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Genetic determinants of statin intolerance

Jisun Oh , R Ban , A Miskie , L Pollex and

A Hegele

Schulich School of Medicine and Dentistry, University of Western

Ontario and Vascular Biology Research Group, Robarts Research

Institute, London, Ontario, Canada N6A 5K8

Lipids in Health and Disease 2007, 6:7 doi:10.1186/1476-511X-6-7

Abstract

Background

Statin-related skeletal muscle disorders range from benign myalgias -

such as non-specific muscle aches or joint pains without elevated

serum creatinine kinase (CK) concentration - to true myositis with >10-

fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The

genetic basis of statin-related muscle disorders is largely unknown.

Because mutations in the COQ2 gene are associated with severe

inherited myopathy, we hypothesized that common, mild genetic

variation in COQ2 would be associated with inter-individual variation

in statin intolerance. We studied 133 subjects who developed myopathy

on statin monotherapy and 158 matched controls who tolerated statins

without incident or complaint.

Results

COQ2 genotypes, based on two single nucleotide polymorphisms (SNP1 and

SNP2) and a 2-SNP haplotype, all showed significant associations with

statin intolerance. Specifically, the odds ratios (with 95% confidence

intervals) for increased risk of statin intolerance among homozygotes

for the rare alleles were 2.42 (0.99 to 5.89), 2.33 (1.13 to 4.81) and

2.58 (1.26 to 5.28) for SNP1 and SNP2 genotypes, and the 2-SNP

haplotype, respectively.

Conclusion

These preliminary pharmacogenetic results, if confirmed, are

consistent with the idea that statin intolerance which is manifested

primarily through muscle symptoms is associated with genomic variation

in COQ2 and thus perhaps with the CoQ10 pathway.

This article is available at http://www.lipidworld.com/content/6/1/7

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