亚甲基四氢叶酸还原酶基因型对叶酸降同型半胱氨酸的影响  

Influence of methylenetetrahydrofolate reductase gene polymorphism on combination of enalapril with folic acid in lowering plasma homocysteine

作　　者：王杨[1] 蒋善群[2] 秦献辉[2] 王旭[2] 徐希平[2] 肖凡凯[3] 赵洛沙[1] 

机构地区：[1]郑州大学第一附属医院心血管内科,河南450052 [2]安徽医科大学生物医学研究所 [3]天津医科大学

出　　处：《中华高血压杂志》2011年第2期143-147,共5页Chinese Journal of Hypertension

摘　　要：背景高血浆同型半胱氨酸(Hcy)水平与亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性是心脑血管疾病的重要危险因素,叶酸降低Hcy水平,从而降低心血管事件已成为心血管领域研究的热点问题,但叶酸、MTHFR基因多态性、Hcy三者之间关系国内外研究的甚少且结论存在差异。目的探讨MTHFR基因C677T多态性对叶酸与依那普利联合用于降低血浆Hcy的影响。方法高血压患者233例随机分配到2个治疗组中,分别接受依那普利(10mg)或依那普利加叶酸(依/叶组,依那普利10mg/叶酸0.4～0.8mg),口服1次/d,疗程8周,观察两组患者血浆Hcy水平的变化,并按MTHFR677CC、CT及TT基因型作分层分析,评估不同基因型对药物降Hcy疗效的作用。结果在依那普利组中,用药8周后TT基因型者血浆Hcy水平上升15%,CC/CT基因型下降2%(P=0.017);在依/叶组中,用药8周后TT型者血浆Hcy水平下降21%,CC/CT型下降9%(P=0.002)。依/叶组TT型对CC/CT型基线Hcy≥10μmol/L发生OR为2.7(P=0.005),8周后OR值下降为2.2(P=0.043)。对血浆Hcy下降幅度进行logistic回归分析,在调整年龄、性别、体质量指数后,依/叶组TT型较CC/CT型个体Hcy水平β值下降2.8(P<0.01);而依那普利组中TT型个体Hcy水平β值升高2.4。结论叶酸与依那普利联合应用能有效降低高血压患者血浆Hcy水平,其中MTHFR基因TT型者获益最大。Background High plasma homocysteine（Hcy）levels and methylenetetrahydrofolate reductase（MTHFR）gene C677T polymorphism are major risk factors for cardiovascular disease.It has become a hot issue in cardiovascular research field that folic acid can have an effect on cardiovascular event reduction by lowering Hcy levels.Nevertheless,there has been little research conducted at home and abroad on the relationships among folic acid,MTHFR gene polymorphism and Hcy.Furthermore,there also exist discrepancies in conclusions.Objective To investigate the influence of MTHFR gene polymorphism on reducing plasma Hcy levels by the combination of enalapril with folic acid in patients with essential hypertension.Methods A total of 233 patients with essential hypertension were randomized into two groups.Group 1 patients were given enalapril 10 mg,once daily,with a period of 8 weeks;while Group 2 patients enalapril plus folic acid at the ratio of 10.0/0.4 mg or 10.0/0.8 mg,once daily,with a period of 8 weeks.The changes in plasma Hcy were observed and analyzed by MTHFR genotypes（TT vs CC/CT）.Results In Group 1,plasma Hcy levels were increased by 15% in TT subjects and decreased by 2% in CC/CT subjects after the 8-week treatment（P =0.017）.In Group 2,plasma Hcy levels lowered by 21% in TT subjects and 9% in CC/CT subjects after the 8-week treatment（P =0.002）.The OR value of baseline Hcy≥10 μmol/L at TT vs CC/CT genotype in Group 2 was 2.7（P =0.005）,and 2.2（P =0.043）respectively before and after the 8-week treatment.In a Logistic analysis for the variable Hcy,the β value was-2.8（P 0.01）for TT subjects in Group 2,the β value was 2.4 for TT subjects in Group 1,after adjusting for age,sex,and body mass index.Conclusion A combination of folic acid and enalapril could effectively decrease the level of plasma Hcy in hypertensives,especially in those with MTHFR genotype TT who are fit for an individualized medical regimen.

关 键 词：亚甲基四氢叶酸还原酶基因 基因多态性 同型半胱氨酸 叶酸 依那普利 

分 类 号：R544.1[医药卫生—心血管疾病]