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

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evalua ted the angiotensin converting enzyme (ACE) and the angiotensin type 1 rece ptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as pos sible 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 o f normal pregnancies were enrolled in this study. Thrombophilic factors, AC E insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G2021 0A and factor V Leiden mutations were analyzed. At univariate and multivari ate 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 hype rhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 9 5% percentile; cut-off, 10.5 mu mol/l per l) was significantly higher in wo men with fetal loss, and an association between Hey and fetal loss was dete cted. All patients showed normal antithrombin, protein C, protein S, and pl asminogen activator inhibitor-1 (PAI-1) values. The presence of one risk fa ctor not associated with others was found in 33 out of 59 patients (56%); A CE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hey. L arge-scale studies are warranted to attribute clinical relevance to these p olymorphisms as risk factors for complicated pregnancies. Blood Coagul Fibr inolysis 11:657-662 (C) 2000 Lippincott Williams & Wilkins.