The angiotensinogen gene M235T polymorphism and development of preeclampsia/eclampsia: A meta-analysis and meta-regression of observational studies

Objectives: The angiotensinogen gene M235T polymorphism is related to an increased risk of hypertension. Hypertension and pregnancy-induced hypertension have been suggested to share common etiologic factors. We examined whether this mutation also increases the risk of preeclampsia/eclampsia. Methods: Pubmed/Medline, Web of Science and EMBASE were searched and a hand search of bibliographies was conducted. In all, 17 studies (including 1446 cases and 3829 controls) published in English between 1993 and October 2006 on the association of angiotensinogen gene M235T polymorphism with preeclampsia/eclampsia were selected. Results: The overall odds ratio (OR) under a random effects model revealed that individuals homozygous for the T allele were 1.62 times more likely to develop preeclampsia/eclampsia [95% confidence interval (CI), 1.12 to 2.33; P = 0.01) compared to individuals homozygous for the M allele. The relation in Caucasians (OR = 1.99; 95% CI, 1.18-3.36; P = 0.01) was similar to that in East Asian populations (OR = 1.74; 95% CI, 0.92-3.28; P = 0.09), although the latter was not statistically significant due to lower numbers of studies. Under additive, recessive and dominant genetic models positive associations were also found. A meta-regression analysis showed that ethnic background was a significant source of between-study heterogeneity (P = 0.04) but design of the study, study size and Hardy-Weinberg equilibrium deviation were not. There was a low probability of publication bias. Conclusion: Our meta-analysis expands the findings on hypertension by showing that the presence of the T allele of the angiotensinogen gene is associated with an increased risk to develop preeclampsia/eclampsia.