Hellenic National Centre for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (HNDC), Athens, Greece.
Cardiovasc Diabetol. 2010 Feb 23;9:10. doi: 10.1186/1475-2840-9-10.
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).
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.
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.
Our findings suggest that variants of ADIPOR2 could be a determinant for atherosclerosis independent of insulin resistance status, possibly by affecting ADIPOR2 protein levels.
脂联素是一种脂肪组织分泌的蛋白，已知具有胰岛素增敏和抗动脉粥样硬化作用。迄今为止，已经发现了两种脂联素受体，即脂联素受体 1（ADIPOR1）和脂联素受体 2（ADIPOR2）。本研究旨在探讨 ADIPOR2 基因变异与冠状动脉疾病（CAD）的关系。
选择跨越 ADIPOR2 基因座的 8 个常见单核苷酸多态性（SNP），以根据冠状动脉造影数据，在希腊人群中进行与人体测量和代谢参数相关的关联研究。它们被分为 CAD（至少一条主要血管狭窄>50%）或非 CAD 个体。使用基于微球的悬浮阵列和等位基因特异性引物延伸（ASPE）方法进行基因分型。使用流式细胞术和实时聚合酶链反应（PCR）分别测定循环 CD14+单核细胞中 ADIPOR2 蛋白和 mRNA 的表达。
ADIPOR2 基因 rs767870 多态性的基因型分布在 CAD 和非 CAD 个体之间存在显著差异（p=0.017）。此外，rs767870 多态性的杂合子与小等位基因的纯合子相比，血流介导的扩张（FMD）值显著降低，内膜-中层厚度（IMT）值更高，外周单核细胞中的 ADIPOR2 蛋白水平增加，调整年龄、性别、腰臀比和 HOMA 后差异有统计学意义。
我们的研究结果表明，ADIPOR2 的变体可能是独立于胰岛素抵抗状态的动脉粥样硬化的决定因素，可能通过影响 ADIPOR2 蛋白水平来实现。
