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亚甲基四氢叶酸还原酶基因多态性与出血性脑卒中相关性的Meta分析 被引量:3

Meta-analysis of the association between methylenetetrahydrofolate reductase gene polymorphisms and hemorrhagic stroke
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摘要 目的:亚甲基四氢叶酸还原酶基因C677T或A1298C位点多态性是否与出血性脑卒中相关存在争议。文章以此评估亚甲基四氢叶酸还原酶基因C677T或A1298C位点多态性与出血性脑卒中的相关性。方法:检索Pub Med、Embase、Web of Science、中国知网、万方数据、维普和中国生物医学服务系统(Sino Med)数据库中的相关文献。由2名人员筛选,提取信息和评价文献质量。建立5种遗传模型:等位基因模型(T vs.C和C vs.A)、显性模型[(CT+TT)vs.CC和(AC+CC)vs.AA]、隐性模型[TT vs.(CC+CT)和CC vs.(AA+AC)]、共显性杂合子模型(CT vs.CC和AC vs.AA)及共显性纯合子模型(TT vs.CC和CC vs.AA)。利用Rev Man5.4和Stata14软件,Cochrane’Q检验和I2值评估异质性,合并OR值和95%CI做为效应及指标,亚组分析探索异质性来源,敏感性分析评估结论稳定性,漏斗图、Begg及Egger检验和剪补法评估发表偏倚。结果:纳入24篇高质量观察性研究文献,其中病例对照研究23篇,横断面研究1篇。(1)亚甲基四氢叶酸还原酶基因C677T位点多态性与出血性脑卒中存在相关性,5种遗传模型均有显著性意义[T vs.C:OR=1.39,95%CI:1.18-1.64;(CT+TT)vs.CC:OR=1.46,95%CI:1.18-1.80;TTvs.(CC+CT):OR=1.54,95%CI:1.20-1.96;CTvs.CC:OR=1.31,95%CI:1.08-1.58;TTvs.CC:OR=1.78,95%CI:1.31-2.43]。亚组分析提示在亚洲人群中亚甲基四氢叶酸还原酶基因C677T与出血性脑卒中存在相关性,而欧洲和非洲则无,随着年龄的增大,其OR值越大,在控制病例组和对照组混杂因素(年龄和性别)的研究中,合并效应量提示相关性有显著性意义;综合各项假阳性结果报告率,推测假阳性可能性较小。(2)亚甲基四氢叶酸还原酶基因A1288C位点多态性与出血性脑卒中相关性无显著性意义[C vs.A:OR=1.16,95%CI:0.98-1.37;(CC+AC)vs.AA:OR=1.19,95%CI:0.96-1.48;CCvs.(AC+AA):OR=1.27,95%CI:0.86-1.88;ACvs.AA:OR=1.04,95%CI:0.71-1.51;CC vs.AA:OR=1.37,95%CI:0.90-2.06];上述位点的亚组分析所得阳性结� OBJECTIVE:Whether the polymorphisms of methylenetetrahydrofolate reductase C677T or A1298C are associated with hemorrhagic stroke is controve rsial.Herein,we evaluate the association between the C677T or A1298C polymorphisms of the methylenetetrahydrofolate reductase gene and hemorrhagic stroke.METHODS:Relevant research literatures were searched in PubMed,Embase,Web of Science,CNKI,WanFang,VIP and SinoMed databases.Two persons screened,extra cted information,and assessed the quality of the literature.Five genetic models were established:allelic model(T vs.C and C vs.A),dominant model [(CT+TT) vs.CC and(AC+CC) vs.AA],recessive model [TT vs.(CC+CT) and CC vs.(AA+AC)],codominant heterozygous models(CT vs.CC and AC vs.AA),and codominant homozygous models(TT vs.CC and CC vs.AA).Analyses were performed using RevMan 5.4 and Stata 14 software,Cochrane’Q test and I2statistics were used to evaluate heterogeneity,and the combined odds ratio(OR) value and its 95% confidence interval(CI) were used as effect indicato rs.Subgroup analyses were performed to explore sources of hete rogeneity,sensitivity analyses to assess the stability of conclusions,and funnel plots,Begg test,Egger test,and trim and fill methods to assess publication bias.RESULTS:Twenty-four high-quality research articles were included,including 23 case-control articles and 1 cross-sectional study.M ethylenetetra hydrofolate reductase C677T polymorphism was associated with hemorrhagic stro ke,and the five genetic models were statistically significant [T vs.C:OR=1.39,95% CI:1.18-1.64;(CT+TT vs.CC:OR=1.46,95% CI:1.18-1.80;TT vs.(CC+CT):OR=1.54,95% CI:1.20-1.96;CT vs.CC:OR=1.31,95% CI:1.08-1.58;TT vs.CC:OR=1.78,95% CI:1.31-2.43].Subgroup analysis suggested that the methylenetetra hydrofolate reductase C677T was associated with hemorrhagic stroke in Asian populations,but not in Europe and Africa.The OR value increased with aging.In studies controlling for confounding factors(age and sex) in case and control groups,pooled effect sizes suggested a statistically sign
作者 朱俊杰 王海煌 李建民 张宇新 刘俊杰 Zhu Junjie;Wang Haihuang;Li Jianmin;Zhang Yuxin;Liu Junjie(School of Clinical Medicine,North China University of Science and Technology,Tangshan 063000,Hebei Province,China;School of Basic Medicine,North China University of Science and Technology,Tangshan 063000,Hebei Province,China;Department of Neurosurgery,Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,Hebei Province,China)
出处 《中国组织工程研究》 CAS 北大核心 2023年第23期3763-3772,共10页 Chinese Journal of Tissue Engineering Research
基金 华北理工大学大学生创新创业训练计划项目(X2021142),项目负责人:朱俊杰 2018年度河北省卫生健康技术研究暨成果转化重点项目(zh2018015),项目负责人:李建民 河北省临床医学优秀人才培养和基础课题研究项目(361036),项目负责人:李建民 唐山市科技计划项目(21130224C),项目负责人:李建民 河北省卫健委医学研究项目(20221533),项目负责人:李建民。
关键词 亚甲基四氢叶酸还原酶基因 MTHFR基因 C677T位点 A1298C位点 基因多态性 出血性脑卒中 META分析 methylenetetrahydrofolate reductase gene MTHFR gene C677T locus A1298C locus gene polymorphism hemorrhagic stroke Meta-analysis
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