中国西北地区人群高同型半胱氨酸血症、亚甲基四氢叶酸还原酶多态性与缺血性脑卒中的关系(英文)

Association of hyperhomocysteinemia and methylenetetrahydrofolate reductase gene polymorphisms with ischemic stroke in Northwest Chinese population

背景:血浆中总同型半胱氨酸水平增高是缺血性脑卒中的一项危险因素,5,10-亚甲基四氢叶酸还原酶是同型半胱氨酸代谢途径中的关键酶。关于5,10-亚甲基四氢叶酸还原酶与缺血性脑卒中的关系还存在争议。目的:通过检测中国西北地区汉族人群中缺血性脑卒中患者血浆中总同型半胱氨酸水平和5,10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型,探讨三者之间的关联性。设计:病例-对照实验。单位:吉林大学第一附属医院神经内科,解放军第四军医大学西京医院神经内科。对象:病例组:随机选取2001-11/2002-05解放军第四军医大学西京医院神经内科经CT或磁共振确诊的缺血性脑卒中患者97例,男71例,女26例。对照组:94例,无脑卒中病史,其中男58例,女36例。以上两组受试者有脑出血,癌症,肾功能障碍及服用维生素和雌激素的排除在外。方法:血浆总同型半胱氨酸水平用全自动荧光偏振免疫分析法检测,5,10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型用聚合酶链式反应-限制性片段多态性分析法检测。主要观察指标:脑卒中患者C677T和A1298C的基因型频率,血浆总同型半胱氨酸水平。结果:677T等位基因在病例组的分布明显高于对照组(59.3%,44.7%,P=0.006),但是1298C等位基因的频率在两组间较接近(22.7%,19.7%,P>0.05)。677TT纯合子与高同型半胱氨酸血症显著相关穴P<0.01雪。Logistic分析表明,C677T突变及高同型半胱氨酸血症者患缺血性脑卒中的OR值分别是1.87和1.03穴P<0.05雪。结论:高同型半胱氨酸血症是缺血性脑卒中的危险因素。C677T基因突变与缺血性脑卒中的发生相关,显著影响血浆总同型半胱氨酸水平,可能是缺血性脑卒中的一个独立的遗传危险因素。

BACKGROUND： It is proposed that elevated serum homocysteine is an important independent risk factor for ischemic stroke （IS）, and 5, 10-methylenetetrahydrofolate reductase （MTHFR） is the key enzyme for homocysteine metabolism. The relationship between genetic mutation of MTHFR and IS remains controversial. OBJECTIVE： To examine the association of hyperhomocysteinemia and two MTHFR gene polymorphisms with IS in Northwest Chinese population. DESIGN： Case-control study. SETTING： Department of Neurology, First Hospital Affiliated to Jilin U- niversity, and Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA. PARTICIPANTS： Ninety-seven consecutive patients with isehemie stroke （71 males and 26 females） treated between November 2001 and May 2002 were recruited, who were diagnosed by CT scan or MRI in the Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA. The control group consisted of 94 subjects （58 males and 36 females） without history of isehemie stroke. All the subjects were free of intraeranial hemorrhage, cancer, renal dysfunction, and none used multivitamins or estrogen. METHODS： Serum homocysteine was measured by fluorescence polarization immunoassay. Polymerase chain reaction-restriction length polymorphism （PCR-RFLP） method was employed to detect the genotype at the two sites of C677T and A1298C in MTHFR gene. MAIN OUTCOME MEASURES： Serum homocysteine levels and the genotypie frequency frequencies of the two mutations of MTHFR. RESULTS： The 677T allele frequency was 59.3% in IS patients and 44.7% in the controls, showing significant differences （P=0.006）, but no difference in 1298C allele frequency was detected between the two groups （22.7% vs 19.7%, P 〉 0.05）. Homozygous 677TT genotype was closely associated with hyperhomocysteinemie （P 〈 0.01）. In multivariate logistic regression analysis, 677T gene mutation and hyperhomocysteinemie were all associated with the IS, with an OR of 1.870 and 1.031 （P 〈 0.05）, respectively. CONCLUSION： Hyperhomocysteinemie is a risk factor of IS, and C677T mutation significantly increases homocysteine levels, and serves also as an independent genetic risk factor of IS.