Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: A meta-analysis of non-family-based studies

The HLA-G 14-bp insertion/deletion polymorphism had been inconsistently associated with recurrent miscarriage (RM) risk. We examined the association by performing a meta-analysis. Eligible articles were searched in PubMed, EMBASE and CNKI without language limitation. We included all the articles about two or more miscarriages associated with HLA-G 14-bp polymorphism. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA10.0 software. 17 studies were included, representing 1786 cases and 1574 controls. The current meta-analysis showed that 14-bp polymorphism was not associated with RM risk in all genetic models and allele contrast(+14 bp vs. -14 bp: OR = 1.13; 95 % CI, 0.96,1.32; +14 bp/+14 bp vs. -14 bp/-14 bp: OR = 1.16, 95 % CI, 0.85, 1.59; +14 bp/-14 bp vs. -14 bp/-14 bp: OR = 1.21, 95 % CI, 0.92,1.58; dominant model: OR = 1.33; 95 % CI, 0.99,1.78; recessive model: OR = 1.06; 95 % CI, 0.79,1.43). Moreover, a significant heterogeneity was evident across studies. On the other hand, the subgroup analysis demonstrated that there was a significant association between HLA-G 14-bp polymorphism and patients with three or more miscarriages(+14 bp vs. -14 bp: OR = 1.27; 95 % CI, 1.04, 1.55; dominant model: OR = 1.52; 95 % CI, 1.16, 1.99; and model +14 bp/-14 bp versus -14 bp/-14 bp: OR = 1.51; 95 % CI, 1.15, 1.97;). Our comprehensive meta-analysis indicated that there was insufficient evidence to demonstrate a conclusive association between the HLA-G 14-bp insertion/deletion polymorphism and the risk of RM. But HLA-G 14-bp insertion/deletion polymorphic variation was associated with RM risk in patients with three or more miscarriages. Larger and well-designed studies may eventually provide a better, comprehensive understanding of the association between the HLA-G 14-bp insertion/deletion polymorphism and RM in the future.