MTHFR基因多肽性及血浆同型半胱氨酸水平与老年人脑卒中发病的关系

Association of polymorphism of MTHFR gene and plasma homocysteine with stroke in Chinese elderly people

目的 :探讨N5,N10 亚甲基四氢叶酸还原酶 (MTHFR)基因C6 77T位点突变和血浆总同型半胱氨酸 (tHcy)水平升高是否增加中国老年人群脑卒中的危险。方法 :对 10 0 2例经头颅CT确诊的老年 (>6 0岁 )脑卒中患者和 94 8例非卒中对照者 ,采用多聚酶链反应 限制性内切酶片段长度多态性技术 (PCR RFLP)检测MTHFRC6 6 7T基因型 ,用高效液相色谱法测定血浆总同型半胱氨酸水平 ,同时所有研究对象记录其病史 ,体检等临床资料及吸烟 ,饮酒等流行病学资料。结果 :脑卒中患者MTHFR基因纯合子突变 (TT)和杂合子突变 (CT)发生率 (6 9 4 % )明显高于对照组 (6 4 3% ,P =0 0 16 ) ,卒中组T等位基因频率 (4 5 8% )也高于对照组 (4 2 4 % ,P =0 0 32 ) ;脑卒中患者血浆总同型半胱氨酸水平及异常检出率和中、重度增高率亦明显高于对照组 (P <0 0 0 1) ,且MTHFR基因TT型 >CT型 >CC型 (P <0 0 0 1)。Logistic回归分析结果显示 :在调整传统危险因素后 ,升高的tHcy水平和CT和TT基因型仍与脑卒中发病的有关 ,且血浆同型半胱氨酸水平越高发生脑卒中的危险性越大。结论 :高同型半胱氨酸血症是中国老年人脑卒中发病的一个独立危险因素 ,而MTHFR基因C6

Objective To investigate whether the genetic mutations of methylenetetrahydrofolate reductase （MTNFR） C677T and elevated plasma total homocysteine （tHcy） increases the risk of stroke in Chinese elderly people. Methods 1002 patients with stroke and 948 controls were recruited. MTHFR genetic C677T polymorphism was de- termined by PCR-RLFP, Plasma total homocysteins levels were measured with high performance liquid chromatography. Data of medical history, physical examination were also collected. Results The frequency of homozygous and hetemzygous MTHFR mutation in stroke patients were higher than in controls （69.4% versus 64.3%, P = 0.016 ）, and frequency of T alleles in stroke patients was higher than in controls （45.4% versus 42.4%, P = 0.032）. The mean plasma tHcy and incidence （ % ） of hyperhomocysteinemia and were significantly higher in stroke group than control group [ 16.21 ± 1.61μmol/L（51.0% ）versus 11.22 ± 1.50μmol/L （37.7%） ; P 〈 0.001 ]. The tHcy concentration was significantly higher in persons with TF genotype than in those with CC or CT. and TF genotype 〉 CT genotype 〉 CC genotype. Multiple stepwise logistic regression analysis showed that elevated tHey levels and TF , CT genotype were still significantly associated with stroke after adjusted the conventional risk factors. Conclusion Hyperhomoeysteinemia is an independent risk factor of stroke in Chinese elderly people, Genetic mutations of MTHFR C677T is possibly important mechanism of hyperhomoeysteinemia and stroke.