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高血压性心脏病患者中基质金属蛋白酶-9基因多态性与心房颤动的关联

Association of MMP-9 gene polymorphisms with atrial fibrillation in hypertensive heart disease patients.

作者信息

Gai Xiaobo, Lan Xiaopeng, Luo Zhurong, Wang Feifei, Liang Yonggang, Zhang Hueimin, Zhang Wenli, Hou Jianping, Huang Mingfang

机构信息

Department of Cardiology, Fuzhou General Hospital, Fuzhou 350025, China.

出版信息

Clin Chim Acta. 2009 Oct;408(1-2):105-9. doi: 10.1016/j.cca.2009.07.020. Epub 2009 Aug 7.

Abstract

BACKGROUND

MMP-9 plays an important role in the pathogenesis of arrhythmogenic atrial remodeling, and may contribute to the development and persistence of atrial fibrillation (AF). Functional polymorphisms in the MMP-9 gene which lead to altered MMP-9 production and/or activity may modulate an individual's susceptibility to AF.

METHODS

A total of 881 hypertensive heart disease patients of Chinese Han population (128 with and 753 without AF) were recruited in this study. The MMP-9 -1562C>T and R279Q genotypes were determined using PCR-RFLP method. The plasma concentration of MMP-9 was measured by ELISA.

RESULTS

Both the genotype distributions and allele frequencies of the -1562C>T polymorphism were significantly different between the AF and control group (P=0.007 and P=0.002, respectively). The T allele carriers (TT + CT) had significantly increased risk of AF compared with the CC homozygotes (OR 1.94, 95% CI 1.20-3.14; adjusted P=0.006) in a logistic regression model after controlling age, left atrial dimension, and the use of angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. The T allele carriers also had increased plasma MMP-9 levels compared with CC homozygotes in both AF patients and control subjects. No relationship between R279Q polymorphism and AF was found in this cohort.

CONCLUSIONS

The -1562C>T polymorphism of MMP-9 gene is significantly associated with AF risk in Chinese Han patients with hypertensive heart disease. The -1562T allele which is associated with increased expression of MMP-9 might be a genetic risk for the development of AF in this cohort.

摘要

背景

基质金属蛋白酶-9(MMP-9)在致心律失常性心房重构的发病机制中起重要作用,可能促进心房颤动(房颤)的发生和持续。MMP-9基因的功能多态性导致MMP-9产生和/或活性改变,可能调节个体对房颤的易感性。

方法

本研究纳入了881例中国汉族高血压心脏病患者(128例有房颤,753例无房颤)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定MMP-9 -1562C>T和R279Q基因型。采用酶联免疫吸附测定(ELISA)法检测血浆MMP-9浓度。

结果

-1562C>T多态性的基因型分布和等位基因频率在房颤组和对照组之间均有显著差异(分别为P=0.007和P=0.002)。在控制年龄、左心房内径以及使用血管紧张素转换酶抑制剂和/或血管紧张素受体阻滞剂后,进行逻辑回归模型分析,发现T等位基因携带者(TT+CT)与CC纯合子相比,房颤风险显著增加(比值比1.94,95%可信区间1.20-3.14;校正P=0.006)。在房颤患者和对照组中,T等位基因携带者的血浆MMP-9水平也高于CC纯合子。在该队列中未发现R279Q多态性与房颤之间存在关联。

结论

MMP-9基因的-1562C>T多态性与中国汉族高血压心脏病患者的房颤风险显著相关。与MMP-9表达增加相关的-1562T等位基因可能是该队列中房颤发生的遗传风险因素。

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