Angiotensinogen gene (met235thr and thr174met), angiotensin-converting enzyme (intron 16 insertion/deletion) and angiotensin II type 1 receptor (A1166C) gene polymorphisms in patients with pre-eclampsia

Abstract

Background: Pre-eclampsia (PE) is a specific disorder of pregnancy characterized by new onset of hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg) and proteinuria (˃0.3g /day), presenting after 20th weeks of gestation. PE affects 2 to 4% of all pregnancies worldwide.

Methods: Ninety-two pre-eclamptic women and ninety-two controls were genotyped using PCR-RFLP and Allele specific PCR analysis. In the present study, we analyzed allelic and genotypic distribution of AGT gene (Met235Thr and Thr174Met), ACE I/D and AT2R1 (A1166C) polymorphisms in patients with PE and healthy controls. Genetic modelling and haplotype analysis was done for these SNPs.

Results: Met235Thr (T704C) polymorphism under dominant and log additive models showed increased risk with pre-eclampsia and reached statistically significant levels for association with the PE but when it was adjusted after Bonferroni correction it became insignificant. While Thr174Met (C521T) polymorphism of AGT gene and AT2R1 A1166C polymorphism did not show any association with PE. ACE I/D polymorphism under recessive model was found significantly associated with the development of PE. While dominant and over dominant models showed protective effect which was also statistically significant.

Conclusion: Met235Thr and ACE I/D polymorphisms are significantly associated with the development of pre-eclampsia, while AT2R1 A1166C and Thr174Met polymorphisms are not associated with the disorder in local population.