The Gene Variants of Maternal/Fetal Renin-Angiotensin System in Preeclampsia: A Hybrid Case-Parent/Mother-Control Study

Abstract

Preeclampsia (PE) is a common pregnancy-related complication, and polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) are believed to contribute to PE development. We implemented a hybrid study to investigate the influence of maternal and fetal ACE I/D, ACE G2350A, AGT M235T, AGT T174M, and AT1R A1166C polymorphisms on PE in Han Chinese women. Polymorphisms were genotyped in 1,488 subjects (256 patients experiencing PE, along with their fetuses and partners, and 360 normotensive controls with their fetuses). Transmission disequilibrium tests revealed that ACE I/D (P = 0.041), ACE G2350A (P = 0.035), and AT1R A1166C (P = 0.018) were associated with maternal PE. The log-linear analyses revealed that mothers whose offspring carried the MM genotype of AGT M235T had a higher risk of PE (OR = 1.54, P = 0.010), whereas mothers whose offspring carried the II genotype of ACE I/D or the GG genotype of ACE G2350A had a reduced risk (OR = 0.58, P = 0.039; OR = 0.47, P = 0.045, respectively). Our findings demonstrate that fetal ACE I/D, ACE G2350A, AGT M235T, and AT1R A1166C polymorphisms may play significant roles in PE development among pregnant Han Chinese women.

The effect of AT1R-1166A/C and AT2R-1675A/G polymorphisms on susceptibility to preeclampsia: A systematic review and meta-analysis

“…[ 60 ] Interestingly, AT1R 1166 C allele was revealed to play a significant role in PE development among Chinese pregnant women. [ 40 ] On the contrary, in some studies, there were no correlation between AT1R -1166 A/C polymorphism and susceptibility to PE. [ 29 , 35 , 51 ] In 2015, a systematic review and meta-analysis by Li et al showed the AT1R -1166 A/C polymorphism was not associated with PIH or PE among a pooled analysis of overall genetic models, [ 61 ] which was consistent with previous results of Zhao et al’ s study.…”

The genetic risk factors for pregnancy‐induced hypertension: Evidence from genetic polymorphisms

“…The important role of RAS is regulating placental development and uteroplacental blood circulation has also been recognized 12 . RAS in the utero‐placental unit of pregnant women affects placental intervillous blood flow and assist in local spiral arterial remodeling 13 . RAS imbalance may result in the potential failure of maternal spiral arterial remodeling and utero‐placental ischemia, ultimately leading to PIH 13 .…”

“…RAS in the utero‐placental unit of pregnant women affects placental intervillous blood flow and assist in local spiral arterial remodeling 13 . RAS imbalance may result in the potential failure of maternal spiral arterial remodeling and utero‐placental ischemia, ultimately leading to PIH 13 . Additionally, RAS monitors blood pressure and body fluids via enzymatic reactions that are controlled through a variety of enzymes and receptors, including renin, angiotensinogen (AGT), angiotensin‐converting enzyme (ACE), angiotensin I (ANG I), angiotensin II (ANG II), angiotensin II receptor type 1 (AT1R), and angiotensin II receptor type 2 (AT2R) 10 .…”

“…13 RAS imbalance may result in the potential failure of maternal spiral arterial remodeling and utero-placental ischemia, ultimately leading to PIH. 13 Additionally, RAS monitors blood pressure and body fluids via enzymatic reactions that are controlled through a variety of enzymes and receptors, including renin, angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin I (ANG I), angiotensin II (ANG II), angiotensin II receptor type 1 (AT1R), and angiotensin II receptor type 2 (AT2R). 10 An array of reactions take place in RAS, through which renin catalyzes AGT and converts it to ANG I, which can be further processed by ACE into ANG II, and ANG II interacts with either AT1R or AT2R to become involved in vasoconstriction, sympathetic activity, cell viability, and aldosterone release.…”

Genetic Association of Angiotensin-Converting Enzyme (ACE) Gene I/D Polymorphism with Preterm Birth in Korean Women: Case-Control Study and Meta-Analysis

“…Angiotensin II stimulates the secretion of aldosterone, which regulates uteroplacental vasoconstriction and blood pressure [9]. Previous studies have shown that an increase in uteroplacental blood pressure is associated with the development of PTB, preeclampsia, and spontaneous abortion [10,11,12].…”