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

Objective: 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.

Methods: 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.

Results: 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;).

Conclusions: 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.