Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C
Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C
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DOI：
10.1016/j.brainresbull.2006.07.014
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发表时间：
2006-12-11
影响因子：
3.8
通讯作者：
Kara, Ihsan
中科院分区：
文献类型：
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作者：
Sazci, Ali;Ergul, Emel;Kara, Ihsan
高同型半胱氨酸血症是缺血性脑卒中的独立危险因素。亚甲基四氢叶酸还原酶（MTHFR）在调节血浆同型半胱氨酸水平中发挥着关键作用。 MTHFR 基因 C677T、A1298C 的两个多态性导致酶活性降低。缺血性和出血性中风的机制尚不清楚。尽管存在争议，但之前的研究已经证明亚甲基四氢叶酸还原酶基因多态性患者的两种中风亚型之间存在因果关系。因此，我们检查了 MTHFR 基因的 C677T 和 A1298C 多态性是否是土耳其白种人群体中缺血性和出血性中风的遗传危险因素。在一项病例对照研究中，使用基于 PCR-RFLP 的方法对 120 名无关中风患者（92 名缺血性中风，28 名出血性中风）和 259 名健康对照者进行了 MTHFR 基因 C677T 和 A1298C 多态性的基因分型。 MTHFR 1298C 等位基因（chi(2) = 8.589；P=0.014）、C1298C 基因型（OR = 2.544；P=0.004）和 C677C/C1298C 复合基因型（OR = 3.020；P = 0.001）与总体卒中相关。 MTHFR 1298C 等位基因（chi(2) = 11.166；P=0.004）、C1298C 基因型（OR=2.950；P=0.001）和 C677C/C1298C 复合基因型（OR=3.463，P=0.0001）与缺血性卒中密切相关。然而有趣的是，MTHFR 677T 等位基因（chi(2) =6.033；P=0.049）、T677T 基因型（OR=3.120；P=0.014）和 T677T/AI298A 复合基因型（OR=4.211；P=0.002）与出血性中风相关。总之，MTHFR 基因的 C677T 和 A1298C 多态性分别是出血性和缺血性中风的遗传危险因素，独立于其他动脉粥样硬化血栓形成危险因素。 (c) 2006 Elsevier Inc. 保留所有权利。
Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2) = 8.589; P=0.014), C1298C genotype (OR = 2.544; P=0.004), and C677C/C1298C compound genotype (OR = 3.020; P = 0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2) = 11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2) =6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/AI298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors. (c) 2006 Elsevier Inc. All rights reserved.