Abstract
Replying to D. F. Carr et al. Nature 513, 10.1038/nature13628 (2014); J. S. Floyd et al. Nature 513, 10.1038/nature13629 (2014)
Our study1 tested for associations of single-nucleotide polymorphisms (SNPs) at the GATM loci with statin-induced myopathy based on the finding that one of these SNPs (rs986699) was associated with statin-induced expression of GATM in a panel of human lymphoblastoid cell lines, and the fact that GATM encodes the enzyme responsible for synthesis of creatine, a major source of energy in skeletal muscle1. Significant associations with incidence of myopathy were found for rs9806699 in statin users from the Marshfield Clinic cohort. Furthermore, significant association was reported in both the Marshfield cohort and in the SEARCH clinical trial of simvastatin treatment for two SNPs in linkage disequilibrium with the index SNP (rs1719247 and rs1346268, r2 > 0.7) that were genotyped in each of these groups. We have extended our meta-analysis to include the study data reported in the accompanying Comments by Carr et al.2 and Floyd et al.3, two studies that individually failed to replicate this association.
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References
Mangravite, L. M. et al. A statin-dependent QTL for GATM expression is associated with statin-induced myopathy. Nature 502, 377–380 (2013)
Carr, D. F. et al. GATM gene variants and statin myopathy risk. Nature 513, http://dx.doi.org/10.1038/nature13628 (2014)
Floyd, J. S. et al. GATM locus does not replicate in rhabdomyolysis study. Nature 513, http://dx.doi.org/10.1038/nature13629 (2014)
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Marciante, K. D. et al. Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet. Genomics 21, 280–288 (2011)
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Mangravite, L., Engelhardt, B., Stephens, M. et al. Mangravite et al. reply. Nature 513, E3 (2014). https://doi.org/10.1038/nature13630
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DOI: https://doi.org/10.1038/nature13630
