Angiotensinogen gene M235T and T174M polymorphisms and susceptibility of pre-eclampsia: a meta-analysis

There are controversies in reports on the association of the angiotensinogen (AGT) gene polymorphisms with the risk of developing pre-eclampsia (PE). We performed a meta-analysis to examine the association between the AGT polymorphisms and PE risk: M235T (31 studies involving 2555 patients and 6114 controls) and T174M (six studies involving 681 patients and 2076 controls). For the M235T polymorphism, the TT genotype increased the PE risk as compared to the MM genotype (odds ratio 1.61, 95% confidence intervals 1.22-2.14, P= 0.001). When stratified by ethnicity, the TT genotype remained significantly associated with higher PE risk in Caucasians and Mongolians but not in Africans. Similar results were also obtained under all three genetic models of the M235T polymorphism. For the T174M polymorphism, no significant association was found in the comparisons (MT vs. TT and MM vs. TT) and under any genetic models. The analysis excluding the highly significant Hardy-Weinberg equilibrium-violating studies and sensitivity analysis further strengthened the validity of these associations. No publication bias was observed in this study. This meta-analysis demonstrates that the AGT M235T polymorphism is significantly associated with PE whereas the T174M polymorphism is not.