This meta-analysis of 23 eligible articles comprehensively and quantitatively evaluated the effects of tumor necrosis factor-α (TNF-α) rs1800629 and rs361525 polymorphisms on sepsis risk. We found that TNF-α rs1800629 was associated with increased sepsis risk in the overall population in four genetic models, including A vs. G (P<0.001, odds ratio (OR)=1.32), GA vs. GG (P<0.001, OR=1.46), GA+AA vs. GG (P<0.001, OR=1.46), and carrier A vs. carrier G (P<0.001, OR=1.32). Subgroup analyses showed a similar result for Asian patients (all P<0.05, OR>1). TNF-α rs361525 was also associated with increased sepsis risk in Asian patients in the four genetic models (all P<0.05, OR>1). Begg's and Egger's tests excluded large publication bias, and sensitivity analysis indicated stable results. Our results suggest that the G/A genotype of TNF-α rs1800629 and rs361525 increases sepsis risk in an Asian population.

Type 1 diabetes (T1D) is a heritable disease associated with multiple genetic variants. This systematic review and meta-analysis assessed the correlation between cytotoxic T-lymphocyte-associated protein 4(CTLA-4) +49A/G polymorphisms and the risk of T1D in children. The random effects model was used to estimate the related odds ratios (ORs) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was used to determine whether the currently available evidence was sufficient and conclusive. Our results indicated that CTLA-4 gene polymorphisms significantly increased the risk of childhood T1D in an allelic model (G vs. A: OR=1.33, 95%CI=1.19-1.48; I2=44.0% and P=0.001for heterogeneity) and a codominant model (GG vs. AA: OR=1.75, 95%CI=1.37-2.24; I2=57.5% and P=0.001for heterogeneity; GA vs. AA: OR=1.26, 95%CI=1.09-1.46; I2=40.4% and P=0.036for heterogeneity). Subgroup analysis results indicated that the ORs were higher in the Asian population (ORallelic model=1.60, ORGG vs. AA=2.46 and ORGA vs. AA=1.58) than the Caucasian population (ORallelic model==1.24, ORGG vs. AA=1.55 and ORGA vs. AA=1.19). The TSA results indicated that the evidence of the effect was sufficient. In conclusion, CTLA4 +49A/G polymorphisms increased the risk of T1D in children, and CTLA4 +49A/G can be considered to be a genetic marker for T1D in children.