Genetic risk factors for placental abruption - A HuGE review and meta-analysis

Background: Although the precise pathophysiology that leads to placental abruption is unknown, there is evidence supporting a genetic etiology. Methods: We searched PubMed and systematically reviewed all case-control studies that investigated the association between genetic variants and placental abruption. Pooled genetic risks were estimated using fixed and random effects odds ratios. Results: Twenty-two articles, examining a total of 14 gene polymorphisms were identified. Seven polymorphisms (F5 Arg506Gln, F5 Met385Thr, F2 G20210A, MTHFR A1298C, MTHFD1 Arg653Gln, NOS3 Glu298Asp, AGT Met235Thr) show significant association in individual studies. Six of the 7 (all except F5Met385Thr) were studied more than once and we therefore included them in our meta-analyses. A positive association under the dominant model was found for the F5 Arg506Gln and F2 G20210A polymorphisms. The random-effects odds ratio for the F5 Arg506Gln polymorphism was 3.4 (95% confidence interval = 1.4-8.3) and the fixed-effects odds ratio for the F2 G20210A polymorphism was 6.7 (3.2-13). Conclusion: Considering the multifactorial etiology of abruption and the relatively small numbers of studies and participants, this review provides only the first clues of possible genetic causes. Larger case-control studies that include gene-gene and gene-environment interactions may help to elucidate the genetics of placental abruption further.