Synergistic effects of angiotensinogen -217 G→A and T704C (M235T) variants on the risk of severe preeclampsia.

Background: The rate-limiting step of the renin-angiotensin system is the enzymatic cleavage of angiotensinogen (AGT) by renin. The aims of the present study were to investigate the association between AGT T704C (M235T) and -217 G→A polymorphisms with the risk of preeclampsia and synergistic effects of both polymorphisms on the susceptibility to preeclampsia.

Methods: We studied AGT variants in 170 women with preeclampsia, including 84 women with mild and 86 women with severe forms of preeclampsia, and 100 age and parity matched controls.

Results: There was a trend towards increased risk of severe preeclampsia in the presence of -217 AA (odds ratio (OR)=1.5, 95% confidence interval (CI)= 0.38-5.84, p=0.57) and TC+CC genotypes (OR=1.32, 95% CI= 0.67-2.58, p=0.42). However, the interaction of both alleles of -217A and 704C highly increased the risk of severe preeclampsia, by 2.23-fold, although this did not reach statistical significance. The frequency of the CC genotype of the T704C polymorphism in early-onset preeclampsia tended to be higher (35%) compared with that in patients with late-onset preeclampsia (21.7%).

Conclusions: The present study demonstrates that both variants of AGT -217 G→A and T704C might work in synergism to influence the risk of severe preeclampsia, which needs to be confirmed in studies with larger sample size.