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Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke

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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.

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Acknowledgments

We gratefully acknowledged the support of the subjects who participated in this study. This study was partly supported by Foundation of Ministry of Education of Hubei Province (D20142102) and Foundation of Taihe Hospital (2013PY02, 2013JJXM011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.

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    1. 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

      Yu-Ming Niu

    2. Center for Evidence-Based and Translational Medicine, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei Province, People’s Republic of China

      Hong Weng & Xiang-Yu Meng

    3. 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

      Chao Zhang & Jie Luo

    4. 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

      Rui-Xia Yuan

    5. 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

      Jin-Zhu Yan

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    Yu-Ming Niu, Hong Weng, and Chao Zhang have contributed equally to this work.

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    Niu, YM., Weng, H., Zhang, C. et al. Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke. Neuromol Med 17, 373–384 (2015). https://doi.org/10.1007/s12017-015-8365-7

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