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血管紧张素转换酶插入/缺失(ACE ID)和亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性在印度北部人群偏头痛遗传易感性中的作用

Role of the ACE ID and MTHFR C677T polymorphisms in genetic susceptibility of migraine in a north Indian population.

作者信息

Joshi Gunjan, Pradhan S, Mittal B

机构信息

Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, (SGPGIMS), Lucknow-226014 (UP) India.

出版信息

J Neurol Sci. 2009 Feb 15;277(1-2):133-7. doi: 10.1016/j.jns.2008.11.002. Epub 2008 Dec 9.

DOI:10.1016/j.jns.2008.11.002
PMID:19081115
Abstract

Migraine is a common debilitating neurovascular disorder. The vascular genes ACE and MTHFR are involved in alterations in vascular endothelium and are suggested to play a role in migraine susceptibility. The aim of our study was to find out the role of ACE ID (rs no. 4646994) and MTHFR C677T (rs no.1801133) polymorphisms in genetic susceptibility of migraine in north Indian population. A total of 150 migraine patients, 220 non-migraine headache patients (Disease controls) and 150 age-sex matched normotensive healthy controls were enrolled for our study. DNA was isolated from peripheral blood leucocytes, and subjected to amplification using specific primers and genotyped using PCR (in case of ACE ID) or PCR-RFLP (in case of MTHFR C677T) methods. chi(2) test was applied for the analysis of genotypic and allelic distributions. Logistic regression analysis was used to find out contribution of genetic polymorphisms to the risk of disease. ACE DD genotype showed significant association in migraine patients with aura (MA) but a marginal significance in female MA patients in comparison with healthy controls. No significant differences in genotype and allelic frequencies of MTHFR C677T polymorphism were found on comparing migraine patients with either disease controls or healthy controls. In contrast, we found synergistic role of ACE (DD)*MTHFR (CT) interaction, showing a positive association in total migraine with aura patients as well as female migraine patients with aura when compared with healthy controls.

摘要

偏头痛是一种常见的使人衰弱的神经血管疾病。血管基因ACE和MTHFR参与血管内皮的改变,并被认为在偏头痛易感性中起作用。我们研究的目的是找出ACE ID(rs编号4646994)和MTHFR C677T(rs编号1801133)基因多态性在印度北部人群偏头痛遗传易感性中的作用。我们的研究共纳入了150例偏头痛患者、220例非偏头痛性头痛患者(疾病对照)和150例年龄和性别匹配的血压正常的健康对照。从外周血白细胞中提取DNA,使用特异性引物进行扩增,并分别采用PCR(针对ACE ID)或PCR-RFLP(针对MTHFR C677T)方法进行基因分型。采用卡方检验分析基因型和等位基因分布。采用逻辑回归分析来确定基因多态性对疾病风险的贡献。ACE DD基因型在有先兆偏头痛(MA)患者中显示出显著关联,但与健康对照相比,在女性MA患者中仅具有边缘显著性。在将偏头痛患者与疾病对照或健康对照进行比较时,未发现MTHFR C677T基因多态性的基因型和等位基因频率存在显著差异。相反,我们发现ACE(DD)*MTHFR(CT)相互作用具有协同作用,与健康对照相比,在所有有先兆偏头痛患者以及女性有先兆偏头痛患者中均显示出正相关。

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