Renin-angiotensin system gene variants and risk of early- and late-onset preeclampsia: A single center case-control study.

ABSTRACT

BACKGROUND: Changes in the renin-angiotensin-aldosterone system's (RAAS) activity due to different genetic variations could represent risk factors for the onset of preeclampsia. OBJECTIVE: To test and quantify the relationships of 8 RAAS gene polymorphisms (angiotensinogen (AGT)-M235T, AGT-T174M, angiotensin converting enzyme (ACE)-I/D, ACE8-A2350G, angiotensin II type 1 receptor (AGTR1)-A1166C, angiotensin II type 2 receptor (AGTR2)-C3123A, renin (REN)-G83A, aldosterone synthase (CYP11B2)-T344C) with susceptibility to early- (EOPE) and late-onset preeclampsia (LOPE). STUDY DESIGN: We performed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis in 217 pregnant women, of whom 87 pregnant women with EOPE/LOPE and 130 normal pregnant women. The relationship between the studied RASS gene polymorphisms and EOPE/LOPE was tested by multiple logistic regressions. RESULTS: The multivariate logistic regression analysis showed that AGT-M235T (adjusted OR = 4.63), AGT-T174M (adjusted OR = 4.13), REN-G83A (adjusted OR = 3) and CYP11B2-C344T (adjusted OR = 3.13) gene polymorphisms remained independent risk factors for EOPE. Moreover, ACE-I/D (adjusted OR = 4.04), ACE-A2350G (adjusted OR = 3.5), AGTR1-A1166C (adjusted OR = 2.73), and REN-G83A (adjusted OR = 2.67) polymorphisms remained independent risk factors for LOPE. The frequency of overweight was significantly different (p = 0.001) in pregnant women with EOPE, LOPE and the control group (LOPE16, 29.6% vs. EOPE12, 36.4% vs. control group16, 12.3%). Pregnant women with EOPE had babies with a significantly lower mean birth weight (2067.9 ±â€¯887.9) in comparison to women with LOPE (mean ±â€¯SD 2860.1 ±â€¯771.1, p < 0.001) and women with normal pregnancies, respectively (mean ±â€¯SD 3324.9 ±â€¯484.9, p < 0.001). CONCLUSION: We confirmed the influence of the renin-angiotensin-aldosterone system through these 8 genetic variations on the onset of preeclampsia.