CKM and LILRB5 Are Associated With Serum Levels of Creatine Kinase

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.