摘要
目的分析亚甲基四氢叶酸还原酶基因(MTHFR)和甲硫氨酸合成酶基因(MTR)多态性与口服叶酸治疗高同型半胱氨酸血症(HHcy)疗效的关系及基因与环境在治疗效果中的交互作用。方法选取2014年6—9月于郑州大学第五附属医院神经内科检查血浆同型半胱氨酸(Hcy)水平的住院HHcy患者515例为研究对象。常规治疗基础上给予口服叶酸(5 mg/d)治疗90 d。治疗中期(叶酸补充45 d)行第1次电话随访,治疗结束(叶酸补充90 d)行第2次电话随访,督促患者遵循医嘱服药,并在治疗结束后到医院复查血浆Hcy水平。按照复查血浆Hcy水平将患者分为失败组(Hcy≥15.0μmol/L)和成功组(Hcy<15.0μmol/L)。收集患者的基线资料,选取MTHFR上2个单核苷酸多态性(SNP)位点和MTR上1个SNP位点,分别为:rs1801133、rs1801131和rs1805087;采用Sequenom公司的时间飞行质谱生物芯片系统(Mass Array系统)检测基因分型和等位基因,采用多因素降维法(MDR)分析基因-环境交互作用。结果随访结束后,剔除服药依从性差或者失访患者131例,剔除两次服药依从性均一般的患者125例,剩余259例。其中失败组115例,成功组144例。失败组患者糖尿病病史发生率、高血压病史发生率、冠心病病史发生率、基线血浆Hcy水平均高于成功组(P<0.05)。成功组3个SNP位点的基因型分布均符合Hardy-Weinberg平衡(rs1801133:χ2=0.11,P=0.170;rs1801131:χ2=0.00,P=1.000;rs1805087:χ2=0.01,P=0.860)。单因素非条件Logistic回归分析结果显示,rs1801133位点的TT基因型、T等位基因,rs1801131位点的AC基因型、AC+CC基因型、C等位基因与叶酸治疗HHcy疗效有回归关系(P<0.05)。MDR软件结果显示,最优模型为高血压病史、冠心病病史和rs1801133的三因素交互模型(P<0.05)。结论 MTHFR rs1801133位点的TT基因型和等位基因T可增加叶酸治疗HHcy失败的风险;rs1801131位点的AC基因型、AC+CC基因型和等位基因C可降低叶酸治疗HHcy失败�
Objective To analyze the relationship between MTHFR and MTR gene polymorphisms and the efficacy of folic acid therapy for hyperhomocysteinemia（HHcy）,and the effect of gene - environment interaction on its efficacy. Methods 515 HHcy patients who had plasma Hcy level measured in the Department of Neurology in the Fifth Affiliated Hospital of Zhengzhou University from June to September 2014 were enrolled as subjects. The subjects were treated with oral folic acid（5 mg/ d）for 90 days. The first and second phone interview was respectively conducted in the medium - term of folic acid treatment at 45 days and at the end of treatment at 90 days. During the period of therapy,patients were urged to follow doctor′s advice and determine plasma Hcy levels after folic acid treatment. According to post - treatment plasma Hcy levels,subjects were divided into the failure group with Hcy≥15. 0 μmol/ L and the success group with Hcy 〈 15. 0 μmol/ L. We collected the baseline information of patients and selected two SNPs in MTHFR（rs1801133 and rs1801131）and one SNP in MTR（rs1805087）. The three SNPs were genotyped by the time - of - flight mass spectrometry（Mass Array system）of Sequenom company. Multifactor dimensionality reduction（MDR）software was used to evaluate gene - environment interaction. Results After the follow - up,131 patients were excluded because of poor compliance or loss to follow - up and 125 patients were eliminated as compliance was general for two times,after which 259 patients remained. The success group and the failure group included 144 patients and 115 patients, respectively. The incidence of history of diabetes,hypertension and coronary heart disease and baseline plasma Hcy levels in the failure group were both higher than the success group（P 〈 0. 05）. The genotype distribution of three SNPs in the success group accorded with Hardy - Weinberg equilibrium（ rs1801133：χ^2 = 0. 11,P = 0. 170;rs1801131：χ^2 = 0. 00,P = 1. 000;rs1805087：χ^2 = 0. 01,P = 0. 860 ） . Si
出处
《中国全科医学》
CAS
CSCD
北大核心
2016年第12期1396-1400,1407,共6页
Chinese General Practice
基金
河南省科技发展计划项目(132102310431)
