Meta-Analysis of Human Leukocyte Antigen-G 3'UTR Polymorphisms Confer Susceptibility to Recurrent Miscarriage

Objectives: The current systematic review and meta-analysis have shown that specific HLA-G 3' UTR variants are associated with recurrent miscarriage (RM). Our aim was to investigate the relevance of HLA-G 3' UTR polymorphisms with the risk of RM. Design: A combined meta-analysis was implemented in this study. Participants/Materials, Setting, Methods: Common electronic databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Cochrane Library, and Google Scholar were used to seek eligible articles up to August 2021. Results: Forty-four eligible articles with 4,467 cases and 3,955 controls were finally enrolled. Our meta-results suggested that 14 bp insertion allele was associated with elevated risk of RM (allelic model: OR = 1.18, 95% CI = 1.07-1.31, p = 0.001). Besides, a significant heterogeneity was observed between studies. Further subgroup analyses based on ethnicity revealed similar positive results in both the Caucasian and Asian subgroups but not in the Middle East subgroup. Moreover, rs1063320 G allele conferred elevated susceptibility to RM in Asian group (allelic model: OR = 1.54, 95% CI = 1.17-2.03, p = 0.002). Additionally, pooled results showed a decreased risk of RM in mothers carrying rs1710 G allele (allelic model: OR = 0.68, 95% CI = 0.55-0.85, p < 0.001) and an increased risk with rs9380142 A allele (allelic model: OR = 1.45, 95% CI = 1.15-1.83, p = 0.002). Further stratified analyses by race showed that these positive results were mainly from the associations observed in Asian populations. Limitations: The main limitation is that the enrolled number of individuals was relatively small. Thus, the results should be cautiously considered. Conclusions: Although the current systematic review and meta-analysis have shown that specific HLA-G 3 & PRIME; UTR variants are associated with RM, a high degree of bias is present and further studies are needed to validate this causative effect.

Automated summary

This study investigated the relevance of HLA-G 3' UTR polymorphisms with the risk of recurrent miscarriage (RM) through a combined meta-analysis. The results showed that specific HLA-G 3' UTR variants, including the 14 bp insertion allele, rs1063320 G allele, rs1710 G allele, and rs9380142 A allele, were associated with an increased or decreased risk of RM in different populations. However, further research is needed to validate these findings and eliminate potential biases.