Correspondence

SLCO1B1 Variants and Statin-Induced Myopathy

N Engl J Med 2009; 360:304January 15, 2009

Article

To the Editor:

Investigators in the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group found one single-nucleotide polymorphism (SNP) in the SLCO1B1 gene that was significantly associated with the risk of development of statin-induced myopathy (P=4×10^–9) (Aug. 21 issue).1 The study was performed in patients with a history of myocardial infarction taking a high dose (80 mg) of simvastatin.

The investigators evaluated other SNPs that have been reported elsewhere as having an association with statin myopathy but could not confirm any significant association in these cases. In our investigation of mutations in 110 patients with severe statin-induced myopathy,2 we found that disease-causing mutations in the gene associated with McArdle's disease (PYGM) and in the carnitine palmitoyltransferase II gene (CPT2) increased by factors of 20 and 13, respectively. Both mutations were of low frequency — 1 in 340 alleles for PYGM and 1 in 540 alleles for CPT2 Known SNPs of high frequency in the PYGM and CPT2 genes that have been associated with a low relative risk of muscle disease were also evaluated by the SEARCH group, which found no association with statin-induced myopathy. This is not a surprising finding considering the low-frequency disease-causing mutations we found to be associated with statin-induced myopathy that could not be effectively captured by the common SNPs examined by the SEARCH group.

Georgirene D. Vladutiu, Ph.D.
Paul J. Isackson, Ph.D.
University at Buffalo, Buffalo, NY 14214
gdv@buffalo.edu

2 References

1. 1

   The SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy -- a genomewide study. N Engl J Med 2008;359:789-799
   Full Text | Web of Science | Medline

2. 2

   Vladutiu GD, Simmons Z, Isackson PJ, et al. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006;34:153-162
   CrossRef | Web of Science | Medline

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