Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase

Nat Commun. 2016 Feb 3;7:10572. doi: 10.1038/ncomms10572.

Abstract

Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH measurements, respectively. Here we describe 13 variants associating with serum CK and 16 with LDH levels, including four that associate with both. Among those, 15 are non-synonymous variants and 12 have a minor allele frequency below 5%. We report sequence variants in genes encoding the enzymes being measured (CKM and LDHA), as well as in genes linked to muscular (ANO5) and immune/inflammatory function (CD163/CD163L1, CSF1, CFH, HLA-DQB1, LILRB5, NINJ1 and STAB1). A number of the genes are linked to the mononuclear/phagocyte system and clearance of enzymes from the serum. This highlights the variety in the sources of normal diversity in serum levels of enzymes.

MeSH terms

  • Anoctamins
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Biomarkers / blood
  • Cell Adhesion Molecules, Neuronal / genetics
  • Chloride Channels / genetics
  • Complement Factor H / genetics
  • Creatine Kinase / blood*
  • Creatine Kinase, MM Form / genetics*
  • Female
  • Gene Frequency
  • Genetic Variation
  • HLA-DQ beta-Chains / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Iceland
  • Isoenzymes / genetics
  • L-Lactate Dehydrogenase / blood*
  • L-Lactate Dehydrogenase / genetics
  • Lactate Dehydrogenase 5
  • Macrophage Colony-Stimulating Factor / genetics
  • Male
  • Nerve Growth Factors / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface / genetics
  • Receptors, Immunologic / genetics
  • Receptors, Lymphocyte Homing / genetics
  • Regression Analysis

Substances

  • ANO5 protein, human
  • Anoctamins
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • CD163L1 protein, human
  • Cell Adhesion Molecules, Neuronal
  • Chloride Channels
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Isoenzymes
  • LILRB5 protein, human
  • NINJ1 protein, human
  • Nerve Growth Factors
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Lymphocyte Homing
  • STAB1 protein, human
  • Complement Factor H
  • Macrophage Colony-Stimulating Factor
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • Creatine Kinase
  • Creatine Kinase, MM Form