title: Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke.
abstract: A number of studies have investigated the association between tumor necrosis factor (TNF)-α gene polymorphisms and ischemic stroke susceptibility. However, results of different individual studies are often inconsistent. To provide a more robust evaluation of the association between polymorphisms of the TNF-α gene and ischemic stroke risk, we performed a systematic review with multivariate meta-analyses. PubMed, Embase, CNKI, and WanFang databases were searched up to December 20, 2014. Two reviewers independently extracted information and assessed quality of included studies after all the eligible studies were identified. Afterward, multivariate meta-analyses were performed using Stata 13. The estimation of polymorphisms and disease risk was presented by odds ratios (ORs) and corresponding 95 % confidence intervals (CIs). Forty-nine eligible case-control studies from 25 articles that explored the association between 10 TNF-α polymorphisms and ischemic stroke were indentified from aforementioned databases. The results of multivariate meta-analysis showed a significant association between -238G/A polymorphism (4760 patients and 4389 controls) and ischemic stroke risk in heterozygotes compared with wild genotype (AG vs. GG: OR 1.44, 95 % CI 1.11-1.87; AA vs. GG: OR 1.98, 95 % CI 0.73-5.40). No significant association of -308G/A, -857C/T, and -1031T/C polymorphisms was observed. The results of stratification analyses of -238G/A polymorphism showed that the AG genotype only increased the risk of ischemic stroke in Asians compared to GG genotype. No additional significant association was observed in this study. In conclusion, the present systematic review and meta-analysis support a prominent role of the TNF-α -238G/A polymorphism in the risk of ischemic stroke in Asian adults only, but do not support the role of -308G/A, -857C/T, -1031T/C, -244G/A, -367G/A, -646G/A, -806C/T, -863C/A, and +448G/A in the risk of ischemic stroke. The current evidence warrants further studies with high quality and large sample size to confirm.
authors.affiliation: Department of Stomatology and Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei Province, People's Republic of China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Niu
authors.affiliation: Center for Evidence-Based and Translational Medicine, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei Province, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Weng
authors.affiliation: Department of Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei Province, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University and Global Health Institute, Wuhan University, 115 Donghu Road, Wuhan, 430071, Hubei Province, People's Republic of China.
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Yuan
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of the Medical College, Shihezi University, 107 Beier Road, Shihezi, 832008, Xinjiang Province, People's Republic of China.
authors.forename: Jin-Zhu
authors.initials: JZ
authors.lastname: Yan
authors.affiliation: Center for Evidence-Based and Translational Medicine, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei Province, People's Republic of China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Meng
authors.affiliation: Department of Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, 442000, Hubei Province, People's Republic of China. taihehospital@yeah.net.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002545:Brain Ischemia / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Ischemic stroke; Meta-analysis; Polymorphism; Systematic reviews; Tumor necrosis factor-alpha