Association of combined genetic variations in PPARγ, PGC-1α, and LXRα with coronary artery disease and severity in Thai population
Association of combined genetic variations in PPARγ, PGC-1α, and LXRα with coronary artery disease and severity in Thai population
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DOI：
10.1016/j.atherosclerosis.2016.03.005
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发表时间：
2016-05-01
期刊：
影响因子：
5.3
通讯作者：
Senthong, Vichai
中科院分区：
文献类型：
--
作者：
Yongsakulchai, Pratthana;Settasatian, Chatri;Senthong, Vichai
背景：动脉粥样硬化是冠状动脉疾病（CAD）的主要病因。过氧化物酶体增殖激活受体- γ (PPAR γ)，肝X受体- α (LXR α)和PPAR γ共激活因子-1 α (PGC-1 α)是调节脂质代谢和动脉粥样硬化相关炎症的核因子。尽管这些核因子的遗传变异与冠心病风险有关联，但这是基于个体基因的，不同种族的结果不一致。我们调查了泰国人群中这些核因子的组合基因多态性与冠心病风险和严重程度的关系。方法：对225例冠心病患者和162例非冠心病患者进行PPAR γ C1431T、PGC-1 α G482S和LXR α -115G/A多态性基因分型。通过bbb50 %狭窄的主血管数量和Gensini评分，研究基因多态性与冠心病风险和冠状动脉粥样硬化严重程度的关系。结果：小等位基因频率分别为21.6% （1431T）、44.8% （482S）和10.7% （-115A）。最初，只有482S等位基因显示与CAD风险[OR = 1.64 (95% CI: 1.01-2.66), P = 0.048]和严重程度[四血管疾病的OR = 1.23 (95% CI: 1.01-1.48), P = 0.036，严重动脉粥样硬化（评分bbb32） = 1.76 (95% CI: 1.05-2.96), P = 0.032]相关。合并1431T/482S和-115GG/482S两种风险基因型也预测CAD的风险[OR = 1.87 (95% CI: 1.09-3.21), P = 0.023, OR = 1.87 (95% CI: 1.15-3.03), P = 0.012]。三种风险基因型的结合进一步增加了冠心病[OR = 2.13 (95% CI: 1.12-4.06), P = 0.022]和严重冠状动脉粥样硬化[OR = 2.09 (95% CI: 1.09-4.02), P = 0.027]的风险。结论：PPAR γ C1431T、PGC-1 α G482S和LXR α -115G/A联合多态性增加了泰国人冠心病的风险，并预测了冠状动脉粥样硬化的严重程度。2016爱思唯尔爱尔兰有限公司版权所有。
Background: Atherosclerosis is a major cause of coronary artery disease (CAD). Peroxisome proliferatoractivated receptor-gamma (PPAR gamma), liver X receptor-alpha (LXR alpha), and PPAR gamma co-activator-1 alpha (PGC-1 alpha) are nuclear factors that regulate lipid metabolism and inflammation implicated in atherosclerosis. Although association of genetic variations in these nuclear factors with CAD risk has been reported, it was based on individual gene with inconsistent results among different ethnicities. We investigated the association of combined gene-polymorphisms of these nuclear factors with the risk and severity of CAD in Thai population.Methods: Hospital-based subjects, 225 CADs and 162 non-CADs, were genotyped for PPAR gamma C1431T, PGC-1 alpha G482S, and LXR alpha -115G/A polymorphisms. Gene-polymorphisms were examined for their association with CAD risk and the severity of coronary atherosclerosis, assessed by both the number of main vessels with >50% stenosis and Gensini score.Results: The minor allele frequencies were 21.6% (1431T), 44.8% (482S), and 10.7% (-115A). Initially, only 482S allele revealed association with CAD risk [OR = 1.64 (95% CI: 1.01-2.66), P = 0.048] and severity [ORs for four-vessel disease = 1.23 (95% CI: 1.01-1.48), P = 0.036, and for severe atherosclerosis (score > 32) = 1.76 (95% CI: 1.05-2.96), P = 0.032]. Combined two risk-genotypes, 1431T/482S and -115GG/482S, also predicted the risk of CAD [OR = 1.87 (95% CI: 1.09-3.21), P = 0.023 and OR = 1.87 (95% CI: 1.15-3.03), P = 0.012 respectively]. The combination of three risk-genotypes further increased the risk of both CAD [OR = 2.13 (95% CI: 1.12-4.06), P = 0.022] and severe coronary atherosclerosis [OR = 2.09 (95% CI 1.09-4.02), P = 0.027].Conclusion: The combined PPAR gamma C1431T, PGC-1 alpha G482S, and LXR alpha -115G/A polymorphisms increased the risk of CAD and predicted the severity of coronary atherosclerosis in Thais. (C) 2016 Elsevier Ireland Ltd. All rights reserved.