Genetic variation in the adiponectin receptor 2 (ADIPOR2) gene is associated with coronary artery disease and increased ADIPOR2 expression in peripheral monocytes.
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.
Halvatsiotis
Iosif
I
Hellenic National Centre for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (HNDC), Athens, Greece.
Tsiotra
Panayoula C
PC
Ikonomidis
Ignatios
I
Kollias
Anastasios
A
Mitrou
Panagiota
P
Maratou
Eirini
E
Boutati
Eleni
E
Lekakis
John
J
Dimitriadis
George
G
Economopoulos
Theofanis
T
Kremastinos
Dimitrios T
DT
Raptis
Sotirios A
SA
D050197:Atherosclerosis / Q000235:genetics; D017023:Coronary Angiography; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D006115:Greece; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood; D054419:Receptors, Adiponectin / Q000097:blood* / Q000235:genetics*; D049629:Waist-Hip Ratio
C475420:ADIPOR2 protein, human; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D054419:Receptors, Adiponectin