CKM and LILRB5 are associated with serum levels of creatine kinase

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Antigens, CD / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Creatine Kinase / blood*
  • Creatine Kinase, MM Form / genetics*
  • Female
  • Gene Frequency
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipidemias / prevention & control
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / genetics
  • Receptors, Immunologic / genetics*

Substances

  • Antigens, CD
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • LILRB5 protein, human
  • Receptors, Immunologic
  • MARK4 protein, human
  • Protein-Serine-Threonine Kinases
  • Creatine Kinase
  • Creatine Kinase, MM Form