Genetic determinants of statin intolerance

Genetic determinants of statin intolerance
Jisun Oh , Matthew R Ban , Brooke A Miskie , Rebecca L Pollex and
Robert 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

Marilyn

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