PPARγ gene C161T substitution is associated with reduced risk of coronary artery disease and decreased proinflammatory cytokine expression
PPARγ gene C161T substitution is associated with reduced risk of coronary artery disease and decreased proinflammatory cytokine expression
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DOI：
10.1016/j.ahj.2007.06.009
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发表时间：
2007-10-01
影响因子：
4.8
通讯作者：
Ma, Aiqun
中科院分区：
文献类型：
--
作者：
Liu, Yu;Yuan, Zuyi;Ma, Aiqun
背景：过氧化物酶体增殖物激活受体γ(PPAR-γ)是一种转录因子，参与动脉粥样硬化相关细胞中促炎症细胞因子的表达，其中肿瘤坏死因子-α(TNF-α)和基质金属蛋白酶(MMPs)等促炎细胞因子的表达是动脉粥样硬化形成过程中的关键步骤。在本研究中，我们检验了PPARγ基因第6外显子C61 T替换对应的多态是否会影响致炎细胞因子的表达和冠状动脉疾病(CADS)的发病。方法研究了247例冠心病患者和214例胸痛综合征患者中PPAR Gamma C16IT替换的分布。结果冠心病患者CC、CT和TT基因频率分别为61.9%、34.0%和4.1%，胸痛综合征患者CC、CT和TT基因频率分别为51.4%、45.3%和3.3%。PPAR-Gamma C161T基因多态性与冠心病显著相关。在Logistic回归模型中，T等位基因携带者(CT+TT)比CC纯合子(优势比0.547，95%CI 0.327~0.831，P=0.012)显著降低了冠心病的风险。与T等位基因携带者相比，CC纯合子也有较高的基质金属蛋白酶-9和肿瘤坏死因子-α水平。结论PPARγC161T基因C161T多态性与冠状动脉造影证实的冠心病相关。PPAR-γ基因的T等位基因可能对冠心病的进展具有保护作用，减少急性冠脉综合征的发生，这可能与冠心病患者基质金属蛋白酶-9和肿瘤坏死因子-α的表达降低有关。
Background Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a transcription factor implicated in the expression of proinflammatory cytokines in atheroma-associated cells, and the expression of proinflammatory cytokines, such as tumor necrosis factor a (TNF-alpha) and matrix metalloproteinases (MMPs), represents a critical step in atherogenesis and atherosclerosis. In this study, we test the hypothesis of whether a polymorphism corresponding to C1 61 T substitution in exon 6 of the PPAR gamma gene may affect the expression of proinflammatory cytokines and the onset of coronary artery diseases (CADs) in a Chinese population.Methods We have studied distribution of the PPAR gamma C 16 IT substitution at exon 6 in 247 patients with CAD and 214 patients with chest pain syndrome. The plasma concentrations of MMP-9 and TNF-a were measured by enzyme-linked immunosorbent assay.Results The results showed that the frequencies of the CC, CT, and TT genotypes were 61.9%, 34.0%, and 4.1% in CAD, and 51.4%, 45.3%, and 3.3% in chest pain syndrome, respectively. There was a significant association between the PPAR gamma C 161 T polymorphism and CAD. The T allele carriers (CT + TT) had significantly reduced CAD risk compared with the CC homozygotes (odds ratio 0.547, 95% Cl 0.327-0.831, P =.012) in a logistic regression model after controlling known independent factors for CAD. The CC homozygotes also had increased MMP-9 and TNF-alpha levels compared with T allele carriers. Moreover, the CC homozygotes were more susceptible to acute coronary syndrome than T allele carriers.Conclusions PPAR gamma C161T polymorphism was associated with angiographically documented CAD in a Chinese population. The T allele of the PPAR gamma gene might have a protective effect on the progression of CAD and reduce the onset of acute coronary syndrome, which might be associated with the decreased expression of MMP-9 and TNF-a in patients with CAD.