肿瘤坏死因子-α基因多态性与肠易激综合征易感性关系的Meta分析

Association between tumor necrosis factor-α gene polymorphisms and susceptibility to irritable bowel syndrome: a Meta-analysis

目的评价肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)基因多态性与肠易激综合征(irritable bowel syndrome,IBS)遗传易感性的关系。方法检索Pub Med、Cochrane Library、Embase、中国期刊全文数据库、中国生物医学文献数据库、万方数据库有关TNF-α基因多态性与IBS易感性的病例-对照研究,检索文献检索时限均从建库至2016年5月30日。采用等位基因模型(G vs.A)、显性遗传模型(GG vs.AA+AG)、隐性遗传模型(AA vs.GG+AG)、共显性遗传模型(GG vs.AG,GG vs.AA)和超显性遗传模型(AG vs.GG+AA)进行分析,以TNF-α308和238基因位点不同遗传模型的相对危险度(odds ratio,OR)值及其95%置信区间(confidence interval,CI)作为效应指标,应用Review Manager 5.3软件对研究结果进行异质性检验和效应值合并分析。结果 7篇原始研究共计3 184例对象(IBS患者1 735例,对照1 449例)被纳入分析,其中涉及TNF-α-308多态性的研究7篇(欧美人种4篇、亚洲人种3篇)、TNF-α-238多态性的研究2篇(均为欧美人种)。应用不同遗传模型分析,结果提示308、238基因位点的等位基因G、A及基因型GG、AG、AA与IBS易感性均无显著相关性(P>0.05)。以临床分型为亚组进行分层分析,结果示308位点等位基因G、A及基因型GG、AG、AA与腹泻型和便秘型IBS易感性均无显著相关性(P>0.05)。以人种为亚组进行分层分析,结果示亚洲人种TNF-α308位点研究资料无统计学异质性,GG vs.AA+AG的OR=1.82,95%CI:1.08~3.07,P=0.02;AG vs.GG+AA的OR=0.50,95%CI:0.29~0.85,P=0.01;GG vs.AG的OR=1.97,95%CI:1.16~3.37,P=0.01,而欧美人种应用不同遗传模型分析后308位点各基因型与IBS易感性无显著相关性。结论亚洲人种TNF-α308位点GG型、AG型基因可能与IBS遗传易感性相关,欧美人种TNF-α308、238位点基因多态性与IBS遗传易感性无显著相关。TNF-α308位点基因多态性与IBS不同亚型易感性无显著相关。

Objective To investigate the association between tumor necrosis factor-a(TNF-a)gene polymorphisms and genetic susceptibility to irritable bowel syndrome(IBS).Methods Publications of case-control studies involving TNF-a gene polymorphisms and susceptibility to IBS from the databases including PubMed,Cochrane Library,EMBase,Chinese National Knowledge Infrastructure(CNKI),Chinese Biological Medical Database(CBM)and Wanfang database were searched up to May30,2016.Five genetic models including allele-contrast(G vs.A),dominant(GG vs.AA+AG),recessive(AA vs.GG+AG),codominant(GG vs.AG,GG vs.AA)and over-dominant models(AG vs.GG+AA)were applied to analyze the odds ratio(OR)and95%confidence interval(Cl)of TNF-a308(A/G)and238(A/G)genetic polymorphism in IBS and control groups.Heterogeneity tests and correlation analyses were performed using Review Manager5.3.Results Seven studies including1735IBS patients and1449controls were selected in this Meta-analysis.There were seven studies focused on TNF-a308polymorphism(four from Europe and Latin America,three from Asia)and two studies on TNF-a238polymorphism(both from Europe and Latin America).The whole-analysis results showed that neither alleles A/G nor the genotypes of GG/AG/AA of TNF-a308/238were associated with the susceptibility to IBS by five genetic models(P>0.05).Further subgroup analyses by different IBS subtypes showed that neither alleles A/G nor the genotypes of GG/AG/AA of TNF-a308were associated with the susceptibility to IBS with diarrhea or constipation.Further subgroup analyses by different populations showed that for TNF-a308polymorphism in Asian population(no statistical heterogeneity),GG vs.AA+AG OR=1.82,95%Cl:1.08-3.07,P=0.02;AGn GG+AA0穴=0.50,95%C/:0.29~0.85,=0.01;GG歡 AG0/?=1.97,95%C/:1.16-3.37,P=0.01.But TNF-a308polymorphism was not significantly associated with the susceptibility to IBS in occidental population.Conclusions TNF-a308GG and AG genotypes may be associated with the genetic susceptibility to IBS in Asian population.No associations are found between the genetic polymorphisms of TNF-a308/238and the genetic susceptibility to IBS in occidental population.The genetic polymorphisms of TNF-a308are not associated with the susceptibility to different subtypes of IBS.