Genetic variation in the adiponectin receptor 2 (ADIPOR2) gene is associated with coronary artery disease and increased ADIPOR2 expression in peripheral monocytes

Cardiovasc Diabetol. 2010 Feb 23:9:10. doi: 10.1186/1475-2840-9-10.

Abstract

Background: Adiponectin is an adipose tissue secreted protein known for its insulin sensitising and anti-atherogenic actions. To this date two adiponectin receptors have been discovered, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). The aim of this study was to investigate the association of ADIPOR2 gene variations with coronary artery disease (CAD).

Methods: Eight common single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR2 locus were chosen to perform association studies with anthropometric and metabolic parameters in a Greek population. They were classified as either CAD (stenosis >50% in at least one main vessel) or non-CAD individuals in accordance with coronary angiography data.Genotyping was performed using a microsphere-based suspension array and the Allele Specific Primer Extension (ASPE) method. Expression of ADIPOR2 protein and mRNA in circulating CD14+ monocytes were determined using flow cytometry and real time Polymerase Chain Reaction assays respectively.

Results: There was a significant difference in the distribution of genotypes of polymorphism rs767870 of ADIPOR2 between CAD and non-CAD individuals (p = 0.017). Furthermore, heterozygotes of the rs767870 polymorphism had significantly lower Flow Mediated Dilatation (FMD) values, higher values of Intima-Media Thickness (IMT) and increased ADIPOR2 protein levels in peripheral monocytes, compared to homozygotes of the minor allele after adjustment for age, sex, waist to hip ratio and HOMA.

Conclusions: Our findings suggest that variants of ADIPOR2 could be a determinant for atherosclerosis independent of insulin resistance status, possibly by affecting ADIPOR2 protein levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / genetics
  • Coronary Angiography
  • Coronary Disease / genetics*
  • Female
  • Flow Cytometry
  • Gene Frequency
  • Greece
  • Heterozygote
  • Homozygote
  • Humans
  • Insulin Resistance
  • Lipids / blood
  • Lipopolysaccharide Receptors / analysis
  • Male
  • Middle Aged
  • Monocytes / chemistry*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / blood
  • Receptors, Adiponectin / blood*
  • Receptors, Adiponectin / genetics*
  • Waist-Hip Ratio

Substances

  • ADIPOR2 protein, human
  • Lipids
  • Lipopolysaccharide Receptors
  • RNA, Messenger
  • Receptors, Adiponectin