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http://purl.uniprot.org/citations/25214527http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25214527http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.org/dc/terms/identifier"doi:10.1161/circgenetics.113.000395"xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Brown A.M."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Diaz A."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Rheaume E."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Bergeron J."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Barhdadi A."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Dube M.P."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Dufour R."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Phillips M.S."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Tardif J.C."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"de Denus S."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Asselin G."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Provost S."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Laplante N."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Turgeon J."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Normand V."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Mongrain I."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Zada Y.F."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Kouz S."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/author"Zetler R."xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/name"Circ Cardiovasc Genet"xsd:string
http://purl.uniprot.org/citations/25214527http://purl.uniprot.org/core/pages"880-886"xsd:string
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