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基质金属蛋白酶-1和基质金属蛋白酶-12基因多态性与突尼斯人群缺血性中风风险

Matrix metalloproteinase-1 and matrix metalloproteinase-12 gene polymorphisms and the risk of ischemic stroke in a Tunisian population.

作者信息

Chehaibi Khouloud, Hrira Mohamed Yahia, Nouira Samir, Maatouk Faouzi, Ben Hamda Khaldoun, Slimane Mohamed Naceur

机构信息

Research Unit: UR 12ES09 Dyslipidemia and Atherogenesis, Faculty of Medicine, Monastir 5019, Tunisia.

Research Unit: UR 07/06, Faculty of Pharmacy, Monastir 5019, Tunisia.

出版信息

J Neurol Sci. 2014 Jul 15;342(1-2):107-13. doi: 10.1016/j.jns.2014.04.036. Epub 2014 May 2.

Abstract

Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, extracellular matrix remodeling, plaque rupture and myocardial infarction. MMP gene polymorphisms contribute to the risk of developing cardiovascular diseases. In this study, we investigated, for the first time, the association between MMP-1-16071G/2G, MMP-12 -82A/G and MMP-12 1082A/G genotypes and haplotypes and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). To examine whether these genetic polymorphisms are associated with susceptibility to IS, 196 patients with IS and 192 controls were examined by PCR-based RFLP. When the analyses were adjusted for multiple risk factors, no interaction between T2DM and MMP-1-1607 1G/2G polymorphism on the risk of ischemic stroke was found (p=0.074). However, MMP-12 polymorphisms genotypes were associated with the higher risk of IS in diabetic patients compared with total patients. The -82G-1082G haplotype of MMP-12 polymorphisms was associated with higher risk of ischemic stroke in diabetic patients [AOR=2.33; 95% CI (1.25-3.62), P=0.032]. These findings showed that there was an important joint effect of the MMP-12 polymorphisms and T2DM on the risk of IS and therefore it can be considered as a potential marker of cerebrovascular disorders in diabetic patients.

摘要

基质金属蛋白酶(MMPs)在早期动脉粥样硬化、细胞外基质重塑、斑块破裂及心肌梗死中发挥重要作用。MMP基因多态性会增加患心血管疾病的风险。在本研究中,我们首次调查了MMP-1 -16071G/2G、MMP-12 -82A/G和MMP-12 1082A/G基因型及单倍型与2型糖尿病(T2DM)患者缺血性卒中(IS)风险之间的关联。为检测这些基因多态性是否与IS易感性相关,采用基于聚合酶链反应的限制性片段长度多态性方法对196例IS患者和192例对照进行检测。在对多种风险因素进行校正分析后,未发现T2DM与MMP-1 -1607 1G/2G多态性在缺血性卒中风险上存在相互作用(p = 0.074)。然而,与所有患者相比,MMP-12多态性基因型与糖尿病患者发生IS的较高风险相关。MMP-12多态性的-82G-1082G单倍型与糖尿病患者缺血性卒中的较高风险相关[AOR = 2.33;95%可信区间(1.25 - 3.62),P = 0.032]。这些研究结果表明,MMP-12多态性与T2DM在IS风险上存在重要的联合效应,因此可将其视为糖尿病患者脑血管疾病的潜在标志物。

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