Format

Send to

Choose Destination
Circ Cardiovasc Genet. 2014 Dec;7(6):880-6. doi: 10.1161/CIRCGENETICS.113.000395. Epub 2014 Sep 11.

CKM and LILRB5 are associated with serum levels of creatine kinase.

Author information

1
From the Montreal Heart Institute, Montreal, Quebec, Canada (M.-P.D., R.Z., A.B., A.M.K.B., I.M., V.N., N.L., G.A., Y.F.Z., S.P., S.d.D., E.R., M.S.P., J.-C.T.); Université de Montréal, Montreal, Quebec, Canada (M.-P.D., R.Z., A.B., R.D., S.d.D., J.T., E.R., M.S.P., J.-C.T.); Beaulieu-Saucier Pharmacogenomics Centre, Montreal, Quebec, Canada (M.-P.D., R.Z., A.B., I.M., A.M.K.B. V.N., G.A., Y.F.Z., S.P., S.d.D., M.S.P., J.-C.T.); Centre Hospitalier du CHU de Québec, Quebec city, Quebec, Canada (J.B.); Centre Hospitalier Régional de Lanaudière, Saint-Charles-Borromée, Quebec, Canada (S.K.); Institut de recherches cliniques de Montréal, Montreal, Quebec, Canada (R.D.); Centre de Santé et de Services Sociaux de Trois-Rivieères, Centre Hospitalier Affilié Universitaire Régional, Trois-Rivières, Quebec, Canada (A.D.); and Centre de recherche du CHUM, Montreal, Quebec, Canada (J.T.). jean-claude.tardif@icm-mhi.org marie-pierre.dube@umontreal.ca.
2
From the Montreal Heart Institute, Montreal, Quebec, Canada (M.-P.D., R.Z., A.B., A.M.K.B., I.M., V.N., N.L., G.A., Y.F.Z., S.P., S.d.D., E.R., M.S.P., J.-C.T.); Université de Montréal, Montreal, Quebec, Canada (M.-P.D., R.Z., A.B., R.D., S.d.D., J.T., E.R., M.S.P., J.-C.T.); Beaulieu-Saucier Pharmacogenomics Centre, Montreal, Quebec, Canada (M.-P.D., R.Z., A.B., I.M., A.M.K.B. V.N., G.A., Y.F.Z., S.P., S.d.D., M.S.P., J.-C.T.); Centre Hospitalier du CHU de Québec, Quebec city, Quebec, Canada (J.B.); Centre Hospitalier Régional de Lanaudière, Saint-Charles-Borromée, Quebec, Canada (S.K.); Institut de recherches cliniques de Montréal, Montreal, Quebec, Canada (R.D.); Centre de Santé et de Services Sociaux de Trois-Rivieères, Centre Hospitalier Affilié Universitaire Régional, Trois-Rivières, Quebec, Canada (A.D.); and Centre de recherche du CHUM, Montreal, Quebec, Canada (J.T.).

Abstract

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); R(2)=0.02) and with the leukocyte immunoglobulin-like receptor subfamily B member 5 (LILRB5) gene (rs2361797: P=1.96×10(-10); R(2)=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); R(2)=0.02) and LILRB5 (rs12975366 P=4.45×10(-10); R(2)=0.01) and statin nonusers (P=4.08×10(-7), R(2)=0.01; P=3.17×10(-9), R(2)=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.

KEYWORDS:

CKM; LILRB5; creatine kinase; genome-wide association study; statin

PMID:
25214527
DOI:
10.1161/CIRCGENETICS.113.000395
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center