Interleukin-18 gene polymorphisms and risk of recurrent pregnancy loss: A systematic review and meta-analysis

Interleukin-18 (IL-18) plays a potential pathological role in recurrent pregnancy loss (RPL). The results of published studies on the relationship between IL-18 gene promoter polymorphisms (-137G/C and-607C/A) and RPL risk remain controversial. This meta-analysis was performed to evaluate the association of IL-18, -137G/C and-607C/A gene polymorphisms with the risk of RPL under recessive, dominant and additive genetic models. A literature search was conducted in Medline, Embase and Web of Science for studies that described the effect of IL-18 gene polymorphisms on RPL risk. The numbers of each -137G/C and-607C/A genotype in the case and control groups were extracted. Quality of the original studies' methodology was also assessed. Meta-analysis was performed using Stata 13.1 software and the fixed effect model was used. Five articles were included in this meta-analysis. No significant heterogeneity between the studies was noted. The IL-18 -137 G/C polymorphism was significantly associated with an increased risk of RPL under a recessive genetic model (CC vs. GG + CG: odds ratio = 1.56, 95% confidence interval = 1.13 ~ 2.15). For the -607C/A mutation, we failed to find any association under any genetic models. The Egger's regression asymmetry test showed no publication bias. Our present study indicates a positive association between the CC genotype of the IL-18 -137G/C gene and RPL risk. Future well-designed large studies are needed to validate the association between IL-18 gene polymorphisms and the risk of RPL.