Association of variant in the ADIPOQ gene and functional study for its role in atherosclerosis

ADIPOQ基因变异的关联及其在动脉粥样硬化中的作用功能研究

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作者:Xinzhong Chen, Yanhong Yuan, Yufeng Gao, Qin Wang, Fei Xie, Dongsheng Xia, Yutao Wei, Ting Xie

Abstract

The burden of atherosclerosis is heritable and associated with elevated risk of developing CVDs. Here, we evaluated genetic variants of adiponectin (ADIPOQ) gene, which has important role in anti- atherosclerosis, with risk of atherosclerosis among a large Chinese population. Our results show that rs74577862 was significantly associated with risk of atherosclerosis (OR=2.08; 95%CI=1.48-2.91; P=2.2×10-5). When stratified by atherosclerosis site, rs74577862 was associated with increased risk of both carotid atherosclerosis (OR=2.03; 95%CI=1.35-3.06; P=6.3×10-4) and coronary atherosclerosis (OR=2.11; 95%CI=1.44-3.09; P=1.1×10-4). In addition, we also carried out site-directed mutagenesis and dual-luciferase reporter assay to confirm the positive finding, which presents a significant decrease in luciferase expression for the reconstructed plasmid with rs74577862 A allele in comparison to the one with G allele (P<0.001). Real-time PCR also confirmed the findings above. These results strongly suggest that the functional SNP, ADIPOQ rs74577862 might contribute to atherosclerosis susceptibility.

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