A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population

Atherosclerosis. 2013 Nov;231(1):158-62. doi: 10.1016/j.atherosclerosis.2013.08.034. Epub 2013 Sep 5.

Abstract

Background: ATP10D belongs to a subfamily of P-type ATPases implicated in phospholipids translocation from the exoplasmic to the cytoplasmic leaflet of cellular biological membrane. Previous genome-wide association study (GWAS) identified that a variant in Atp10d gene (rs2351791) associates with serum lipid profile and myocardial infarction. The objective of this study is to assess the effect of this variant on atherosclerosis in Japanese elderly population.

Method: Consecutive autopsy cases registered in JG-SNP study were recruited (n = 1536). The samples were pathologically assessed for atherosclerosis using macroscopic examination of the formalin-fixed arteries, and coronary stenotic index (CSI), intracranial atherosclerotic index (ICAI) and pathological atherosclerotic index (PAI), which represent systemic arteries were calculated. The variant rs2351791 (G/T) in Atp10d gene was genotyped by Taqman genotyping assay and association determined.

Result: Both CSI and ICAI were significantly higher in GG genotype than GT genotype and TT genotype (p = 0.003 and p = 0.001, respectively). Both associations remained significant in minor allele dominant model after adjusting for age, hypertension, diabetes, HDL, smoking and drinking (p = 0.001 and p = 0.001, respectively). PAI was not associated with this variant. Consistent with the previous report, plasma HDL cholesterol level was lower in GG genotype compared to GT + TT genotypes (p = 0.001).

Conclusion: The rs2351791 SNP in the Atp10d gene affects the susceptibility for cardiac and intracranial vascular stenosis in the elderly Japanese population.

Keywords: ATPase, class V, type 10D,; Atp10d; CSI; Cardiac stenotic index; HDL; High density lipoprotein; ICAI; Intracranial artherosclerotic index; PAI; Pathological atherosclerotic index; Single nucleotide polymorphism (SNP); cardiac stenotic index; high density lipoprotein; intracranial atherosclerotic index; pathological atherosclerotic index.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Atherosclerosis / genetics*
  • Cerebrovascular Disorders / genetics
  • Cholesterol, HDL / blood
  • Coronary Stenosis / genetics*
  • Genetic Association Studies
  • Humans
  • Membrane Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide

Substances

  • Cholesterol, HDL
  • Membrane Transport Proteins
  • Adenosine Triphosphatases
  • ATP10A protein, human