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.