Association of Tumor Necrosis Factor-α (TNF-α) -308G>A and -238G>A Polymorphisms with Recurrent Pregnancy Loss Risk: A Meta-Analysis

Background: Studies have been carried out to evaluate the association of tumor necrosis factor-α (TNF-α) gene promoter region polymorphisms with recurrent pregnancy loss (RPL) risk. However, the results remain controversial and incomplete. Hence, we performed a meta-analysis to evaluate the association of TNF-α -308G>A and -238G>A polymorphisms with RPL risk. Materials and Methods: A comprehensive search of PubMed, Web of Knowledge and EMBASE was performed to identify relevant studies up to December 1, 2017. The associations was assessed by odds ratios (OR) and the corresponding 95% confidence interval (CI). Results: A total of 29 case-control studies, including 20 studies on TNF-α -308G>A (3,461 cases and 3,895 controls) and nine studies on TNF-α -238G>A (2,589 cases and 2,664 controls), were included in the meta-analysis. Overall, we found TNF-α -308G>A polymorphism can increase RPL risk under the homozygote (OR = 1.716, 95% CI 1.210-2.433, p= 0.002) and the recessive model (OR = 1.554, 95% CI 1.100-2.196, p= 0.012). The results showed that TNF-α -238 G>A polymorphism was significantly associated with increased risk of RPL under the allele model (OR = 1.554, 95% CI 1.100-2.196, p= 0.012). Stratified analysis revealed that there was a significant association between the TNF-α -308G>A polymorphism and increased RPL risk in Asians under the homozygote (OR=2.190, 95% CI 1.465-3.274, p≤0.001), the dominant (OR = 1.642, 95% CI 1.269-2.125, p≤0.001) and the recessive (OR=1.456, 95% CI 1.039-2.040, p=0.029) models, but not in Caucasians. A non-significant association between TNF-α -238G>A and RPL risk was identified by ethnicity. Moreover, TNF-α -308G>A and -238G>A polymorphisms were significantly associated with increased risk of RPL in high quality studies and RFLP-PCR subgroups. Conclusion: The present meta-analysis demonstrates that TNF-α -308G>A and -238G>A polymorphisms are associated with risk of RPL.