同型半胱氨酸与中风风险：亚甲基四氢叶酸还原酶C677T多态性及叶酸干预的修饰作用
Homocysteine and Stroke Risk: Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention.
作者信息
Zhao Min, Wang Xiaobin, He Mingli, Qin Xianhui, Tang Genfu, Huo Yong, Li Jianping, Fu Jia, Huang Xiao, Cheng Xiaoshu, Wang Binyan, Hou Fan Fan, Sun Ningling, Cai Yefeng
机构信息
From the National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.Z., X.Q., B.W., F.F.H.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Neurology, First People's Hospital, Lianyungang, China (M.H.); Institute for Biomedicine, Anhui Medical University, Hefei, China (G.T.); Department of Cardiology, Peking University First Hospital, Beijing, China (Y.H., J.L.); Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, China (J.F.); Department of Cardiovascular Medicine, Second Affiliated Hospital of Nanchang University, Jiangxi, China (X.H., X.C.); Hypertension Research Laboratory of Heart Center, Peking University People's Hospital, Beijing, China (N.S.); and Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (M.Z., Y.C.).
出版信息
Stroke. 2017 May;48(5):1183-1190. doi: 10.1161/STROKEAHA.116.015324. Epub 2017 Mar 30.
BACKGROUND AND PURPOSE
Elevated blood homocysteine concentration increases the risk of stroke, especially among hypertensive individuals. Homocysteine is largely affected by the methylenetetrahydrofolate reductase C677T polymorphism and folate status. Among hypertensive patients, we aimed to test the hypothesis that the association between homocysteine and stroke can be modified by the methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention.
METHODS
We analyzed the data of 20 424 hypertensive adults enrolled in the China Stroke Primary Prevention Trial. The participants, first stratified by methylenetetrahydrofolate reductase genotype, were randomly assigned to receive double-blind treatments of 10-mg enalapril and 0.8-mg folic acid or 10-mg enalapril only. The participants were followed up for a median of 4.5 years.
RESULTS
In the control group, baseline log-transformed homocysteine was associated with an increased risk of first stroke among participants with the CC/CT genotype (hazard ratio, 3.1; 1.1-9.2), but not among participants with the TT genotype (hazard ratio, 0.7; 0.2-2.1), indicating a significant gene-homocysteine interaction (=0.008). In the folic acid intervention group, homocysteine showed no significant effect on stroke regardless of genotype. Consistently, folic acid intervention significantly reduced stroke risk in participants with CC/CT genotypes and high homocysteine levels (tertile 3; hazard ratio, 0.73; 0.55-0.97).
CONCLUSIONS
In Chinese hypertensive patients, the effect of homocysteine on the first stroke was significantly modified by the methylenetetrahydrofolate reductase C677T genotype and folic acid supplementation. Such information may help to more precisely predict stroke risk and develop folic acid interventions tailored to individual genetic background and nutritional status.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.
背景与目的
血液中同型半胱氨酸浓度升高会增加中风风险，尤其是在高血压患者中。同型半胱氨酸在很大程度上受亚甲基四氢叶酸还原酶C677T基因多态性和叶酸状态的影响。在高血压患者中，我们旨在检验如下假设：同型半胱氨酸与中风之间的关联可通过亚甲基四氢叶酸还原酶C677T基因多态性和叶酸干预加以改变。
方法
我们分析了纳入中国脑卒中一级预防试验的20424名高血压成年人的数据。参与者首先按亚甲基四氢叶酸还原酶基因型进行分层，然后被随机分配接受10毫克依那普利和0.8毫克叶酸的双盲治疗或仅接受10毫克依那普利治疗。参与者的中位随访时间为4.5年。
结果
在对照组中，基线经对数转换的同型半胱氨酸与CC/CT基因型参与者首次中风风险增加相关（风险比，3.1；1.1 - 9.2），但与TT基因型参与者无关（风险比，0.7；0.2 - 2.1），表明存在显著的基因 - 同型半胱氨酸相互作用（P = 0.008）。在叶酸干预组中，无论基因型如何，同型半胱氨酸对中风均无显著影响。同样，叶酸干预显著降低了CC/CT基因型且同型半胱氨酸水平高的参与者（第3三分位数）的中风风险（风险比，0.73；0.55 - 0.97）。
结论
在中国高血压患者中，亚甲基四氢叶酸还原酶C677T基因型和叶酸补充显著改变了同型半胱氨酸对首次中风的影响。此类信息可能有助于更精确地预测中风风险，并制定针对个体遗传背景和营养状况的叶酸干预措施。
Zotero 插件