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醛脱氢酶 2 Glu504lys 多态性在急性冠状动脉综合征中的作用。

Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome.

机构信息

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Ji'nan, [corrected] China.

出版信息

J Cell Mol Med. 2011 Sep;15(9):1955-62. doi: 10.1111/j.1582-4934.2010.01181.x.

Abstract

This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30-50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31-2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23-2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs.

摘要

这项研究旨在探讨乙醛脱氢酶 2(ALDH2)Glu504Lys 多态性与急性冠状动脉综合征(ACS)风险的关联。我们纳入了 1092 名无亲缘关系的汉族人,其中 546 人患有 ACS,546 人年龄和性别匹配作为对照组。携带 ALDH2 突变基因型的受试者发生 ACS 的比例明显高于对照组(46.7% vs. 31.9%,P<0.001)。Logistic 回归分析显示,ALDH2 突变独立与 ACS 相关(比值比[OR]1.95,95%置信区间[CI]:1.31-2.92,P=0.001),但在调整饮酒因素后,其相关性减弱(OR 1.82,95%CI:1.23-2.70,P=0.003)。在原发性 ST 段抬高型心肌梗死(STEMI)患者的亚组分析中也得到了类似的结果。在 ACS 患者(P=0.002)和对照组(P=0.009)中,ALDH2 突变与高敏 C 反应蛋白(hs-CRP)水平显著相关,与循环内皮祖细胞(EPC)数量显著相关(P=0.032);此外,将 hs-CRP 水平和 EPC 数量作为回归分析中的独立变量,降低了 ALDH2 多态性在 ACS 或原发性 STEMI 中的重要性。然而,ALDH2 多态性与存在显著狭窄的冠状动脉数量、Gensini 评分或肱动脉血流介导的舒张功能无相关性。我们的研究结果表明,ALDH2 突变是 ACS 的遗传风险标志物,其部分原因与饮酒、炎症和循环 EPC 数量有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fe1/3918050/26b7b9677f83/jcmm0015-1955-f1.jpg

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