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

Background: Multiple studies have been carried out examining the association of tumor necrosis factor-α gene (TNF-α) promoter region polymorphisms with recurrent pregnancy loss (RPL) risk. However, the results remain con- troversial and incomplete. Hence, we performed a meta-analysis to evaluate the association of the TNF-α -308G>A and -238G>A polymorphisms with RPL risk.
Materials and Methods: In this meta-analysis, a comprehensive search of PubMed, Web of Knowledge and EM- BASE was performed to identify relevant studies published until December 1, 2017. The associations were assessed by odds ratio (OR) and its corresponding 95% confidence interval (CI).
Results: A total of 29 case-control studies, comprising 20 studies on TNF-α -308G>A (3,461 cases and 3,895 con- trols) and nine studies on TNF-α -238G>A (2,589 cases and 2,664 controls), were included in the meta-analysis. Over- all, we found TNF-α -308G>A to be associated with an increase in RPL risk under the homozygote (OR=1.716, 95% CI: 1.210-2.433, P=0.002) and the recessive (OR=1.554, 95% CI: 1.100-2.196, P=0.012) models. TNF-α -238G>A was also 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 a more 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 was, however, identified between TNF-α -238G>A and RPL risk based on ethnicity. Moreover, TNF-α -308G>A and -238G>A polymorphisms were significantly associated with in- creased risk of RPL in high quality studies and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) subgroups.
Conclusion: The present meta-analysis demonstrates that TNF-α -308G>A and -238G>A polymorphisms are associ- ated with an increased risk of RPL.