Tumor necrosis factor-alpha gene polymorphisms and susceptibility to ischemic heart disease: A systematic review and meta-analysis

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A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and ischemic heart disease (IHD) risk. However, the results remained controversial. Therefore, we performed a systematic review with multiple meta-analyses to provide the more precise estimations of the relationship.


We systematically searched electronic databases (PubMed, the Web of Science, EMBASE, Medline, Chinese National Knowledge Infrastructure, WanFang and ChongQing VIP Database) for relevant studies published up to February 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for assessing the association. The present meta-analysis was performed using STATA 12.0 software.


In total, 45 articles with 17,375 cases and 15,375 controls involved were included. Pooled ORs revealed a significant association between TNF-α −308G/A gene polymorphism and IHD (A vs. G: OR = 1.22, 95% CI = 1.10–1.35; (AA + GA) vs. GG: OR = 1.18, 95% CI = 1.03–1.36; (AA vs. (GA+GG): OR = 1.37, 95% CI = 1.08–1.75)), indicating that the TNF-α −308A allele might be an important risk factor for IHD. No association between other TNF-α gene polymorphisms and susceptibility to IHD were observed. No publication bias were found. Sensitivity analyses indicated that our results were stable.


The present study indicated a possible association between the TNF-α −308G/A gene polymorphism and IHD risk. However, evidence was limited to confirm the role of TNF-α −238G/A, −857C/T, −863C/A, −1031T/C and other TNF-α gene polymorphisms in the risk of IHD.

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