Maternal genetic polymorphisms and unexplained recurrent miscarriage: a systematic review and meta-analysis

The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. However, the results of these studies were inconsistent, especially when conducted in different populations. Therefore, we performed the current study to systematically review the broad spectrum of genetic polymorphisms that were suspected to be involved in RM, and discussed potential genetic biomarkers of RM. Eligible articles were identified in PubMed, Medline, Embase and CNKI. Odd ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association, and a probability value (p value) of 0.05 or less was considered as statistically significant. A total of 425 eligible articles were included in this systematic review and 369 articles evaluating 124 polymorphisms of 73 genes were meta-analyzed. Significant associations were found between RM and 53 genetic polymorphisms of 37 genes. Our findings suggest that genetic variants of HLA-G, IFNG, TNF, IL-6, IL-10, FII, FV, FXIII, ITGB3, MTR, MTHFR, PAI-1, NOS3, KDR, TP53, VEGFA, CYP17, CYP1A1, CYP2D6, ANXA5, and XCI may serve as biological markers of RM. This study indicates that over-active immunological responses, thrombophilia, abnormal placental function, and disturbance of metabolic regulation may be implicated in the pathogenesis of RM.