Association of Angiotensinogen M235T Gene variants, and Plasma Renin Activity with Preeclampsia

Abstract

Article History Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin- angiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the most common polymorphisms of the renin- angiotensin system genes with preeclampsia we have examined 50 women with preeclampsia and 50 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), plasma renin was determined by enzyme linked immunosorbent assay (ELISA). Plasma renin was significantly decreased in patients with preeclampsia compared with normotensive pregnant women. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia. In preeclampsia group the frequency of AGT gene, M235T misssense mutation was 92% (18% were heterozygous and 82%were homozygous), compared with 56% in control group (34% heterozygous, 66% homozygous). In preeclampsia group the frequency of M allele; 17% (n=13) versus 61% (n=39) for the control group, while the frequency of T allele in preeclampsia group; 83% (n=47) versus 39% (n=28) for the control group. Furthermore, there was a positive risk of developing preeclampsia when having TT genotype, and the results were highly statistically significant (odd ratio=2.597, X 2 = 16.39, P =0.00) for TT genotype compared to MM genotype. There was significant positive correlation between plasma renin activity and mean arterial pressure (MAP) (r= 0.9, p= 0.000). There was no statistical significance between plasma renin activity and age in preeclampsia group (r= 0.044, p= 0.759). In conclusion, an increased risk for preeclampsia in women carrying the TT genotype of the AGT gene was observed. Plasma renin activity was significantly decreased in patients with preeclampsia.