Genes Implicated in Myopathy in Individuals on Simvastatin
Common variants in SLC01B1 strongly linked with higher risk
WEDNESDAY, July 23 (HealthDay News) -- Variants in the SLC01B1 gene, which plays a role in the hepatic uptake of statins, may raise the risk of myopathy in individuals taking simvastatin, according to research published online July 23 in the New England Journal of Medicine.
Writing on behalf of the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) Collaborative Group, the authors analyzed data from a genomewide association study in 85 subjects who had myopathy or were considered to have incipient myopathy based on their blood profile, and 90 matched controls without myopathy, all of whom were taking 80 mg of simvastatin daily.
The researchers found that the single-nucleotide polymorphism (SNP) rs4363657 within SLC01B1 was strongly associated with myopathy. In addition, more than 60 percent of the cases could be attributed to the C variant of the rs4149056 SNP; the odds ratio for myopathy was 16.9 in CC homozygotes compared with TT homozygotes.
"The degree of myopathy that occurred was mild and reversible, in stark contrast to a form of statin-induced rhabdomyolysis that involves severe muscle damage accompanied by toxic effects in other organs such as the kidney. SLC01B1 variants must be tested for an association with this adverse drug reaction as soon as possible," writes Yusuke Nakamura, M.D., Ph.D., of the University of Tokyo in Japan, in an accompanying editorial. "However a global network for the collection of data on persons with statin-induced rhabdomyolysis would be required to test for the association with a variant in SLC01B1."
The SEARCH trial was funded by a grant from Merck, and the Heart Protection Study -- used for testing replication in this article -- was funded by grants from organizations including Merck and Roche Vitamins.