Angiotensin-converting enzyme DD genotype, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase first-trimester fetal-loss susceptibility

Abstract

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evaluated the angiotensin converting enzyme (ACE) and the angiotensin type 1 receptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as possible risk factors for fetal loss. Fifty-nine women with a history of three or more first-trimester fetal losses and 70 healthy women with a history of normal pregnancies were enrolled in this study. Thrombophilic factors, ACE insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G20210A and factor V Leiden mutations were analyzed. At univariate and multivariate analysis, a significant association between ACE DD and AT1R CC genotype and fetal loss was observed. The effect of the ACE DD genotype on the risk of fetal loss was higher in AT1R C allele carriers. The prevalence of hyperhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 95% percentile; cut-off, 10.5 micromol/l per l) was significantly higher in women with fetal loss, and an association between Hcy and fetal loss was detected. All patients showed normal antithrombin, protein C, protein S, and plasminogen activator inhibitor-1 (PAI-1) values. The presence of one risk factor not associated with others was found in 33 out of 59 patients (56%); ACE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hcy. Large-scale studies are warranted to attribute clinical relevance to these polymorphisms as risk factors for complicated pregnancies.

Angiotensin-converting enzyme insertion/deletion (I/D) polymorphisms and recurrent pregnancy loss: a meta-analysis

“…The known aetiologic factors for RPL include parental chromosome abnormalities, endocrinological disorders, hereditary thrombophilia, immunologic factors, male factors, and environmental factors. In addition, the ACE I/D polymorphism has been found to be associated with the disease and the hypofibrinolytic disorders [11,12]. Although the exact factors for RPL are not confirmed, the inherited predisposition to thrombophilia may be one of the main causes according to some studies [13][14][15][16][17].…”

“…While reading the full texts, the following articles were removed: two studies did not meet Hardy-Weinberg equilibrium (P 0 0.0003 and P 0 0.0217, respectively) [25,26]; one study could not extract the allele data (ACE I/D in RPL) from its groups [27]; one study was not only focused on RPL, but also on pre-eclampsia and foetal growth restriction which made it hard to get the data required [28]; and the other two studies included the data of case and control groups, but little information about the ACE I/D polymorphism [16,29]. Finally, there were 9 studies meeting the inclusion criteria that were included [11,[30][31][32][33][34][35][36][37]. Among the collected studies, five investigated Caucasian populations [11,30,31,34,37], and the others investigated Asian patients [33,34,36,37].…”

“…Finally, there were 9 studies meeting the inclusion criteria that were included [11,[30][31][32][33][34][35][36][37]. Among the collected studies, five investigated Caucasian populations [11,30,31,34,37], and the others investigated Asian patients [33,34,36,37]. They were located in Italy, China, USA, Gaza Strip, Iran and Turkey.…”

“…The case populations had no history of chronic infections, thromboses, autoimmune diseases, endocrinologic disorders, a After the sensitive analysis, remove the article of heterogeneity. [30] or congenital anomalies [11,[30][31][32][33][34][35][36][37]. All of the cases came from the hospital, and the controls were limited to patients having delivered at least one healthy, term infant with no history of pregnancy loss or healthy volunteers.…”

Low-Molecular-Weight Heparin Lowers the Recurrence Rate of Preeclampsia and Restores the Physiological Vascular Changes in Angiotensin-Converting Enzyme DD Women

“…14 ACE is involved in key events of hemostasis and of inflammatory process 15 related to preeclampsia, in addition to its involvement in modulating vascular tone and smooth muscle cell proliferation.…”