Dube M.-P.,Montreal Heart Institute |
Dube M.-P.,University of Montreal |
Dube M.-P.,Beaulieu Saucier Pharmacogenomics Center |
Zetler R.,Montreal Heart Institute |
And 35 more authors.
Circulation: Cardiovascular Genetics | Year: 2014
Background-Statins (HMG-CoA reductase inhibitors) are the most prescribed class of lipid-lowering drugs for the treatment and prevention of cardiovascular disease. Creatine kinase (CK) is a commonly used biomarker to assist in the diagnosis of statin-induced myotoxicity but the normal range of CK concentrations is wide, which limits its use as a diagnostic biomarker. Methods and Results-We conducted a genome-wide association study of serum CK levels in 3412 statin users. Patients were recruited in Quebec, Canada, and genotyped on Illumina Human610-Quad and an iSelect panel enriched for lipid homeostasis, hypertension, and drug metabolism genes. We found a strong association signal between serum levels of CK and the muscle CK (CKM) gene (rs11559024: P=3.69×10-16; R2=0.02) and with the leukocyte immunoglobulin-like receptor subfamily B member 5 (LILRB5) gene (rs2361797: P=1.96×10-11; R2=0.01). Genetic variants in those 2 genes were independently associated with CK levels in statin users. Results were successfully replicated in 5330 participants from the Montreal Heart Institute Biobank in statin users for CKM (rs11559024: P=4.32×10-16; R2=0.02) and LILRB5 (rs12975366 P=4.45×10-10; R2=0.01) and statin nonusers (P=4.08×10-7; R2=0.01; P=3.17×10-9; R2=0.02, respectively). Conclusions-This is the first genome-wide study to report on the underlying genetic determinants of CK variation in a population of statin users. We found statistically significant association for variants in the CKM and LILRB5 genes. © 2014 American Heart Association, Inc. Source