ORIGINAL RESEARCH ARTICLE Renin Angiotensin System Blockage Associates with Insertion/Deletion Polymorphism of Angiotensin-Converting Enzyme in Patients with Hypertensive Emergency Jose ´ F. Vilela-Martin, 1 Renan O. Vaz-de-Melo, 1 Luciana N Cosenso-Martin, 1 Cristina H. Kuniyoshi, 1 Juan C. Yugar-Toledo, 1 Marcela A.S. Pinhel, 2 Gisele F. de Souza, 2 Dorote ´ ia R. S. Souza, 2 Eduardo Pimenta, 3 Heitor Moreno Ju ´ nior, 4 and Jose ´ P. Cipullo 1 Hypertensive crisis (HC) stands out as a form of acute elevation of blood pressure (BP). It can manifest itself as hypertensive emergency (HE) or hypertensive urgency (HU), which is usually accompanied with levels of diastolic BP ‡ 120 mmHg. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism may influ- ence manifestations of HC. Thus, this study evaluated the influence of ACE I/D polymorphism in individuals with HC. A total of 187 patients admitted with HC (HU [n = 69] and HE [n = 118]) and 75 normotensive individuals were included in the study. Peripheral blood was drawn for a biochemical and genetic analysis of the ACE I/D poly- morphism by Polymerase Chain Reaction. HC group showed higher systolic BP, body mass index (BMI), glycemia, creatinine, and lower high-density lipoprotein (HDL) cholesterol compared with normotensive individuals. The use of renin–angiotensin system (RAS) blockers was more frequent in the HU group than in the HE group ( p = 0.020). The II genotype was more predominant in normotensive and HU individuals than among HE individuals (18.7%, 11.6%, and 2.5%, respectively; p = 0.004). Higher BMI and glycemia were associated with HC in the logistic regression model. ACE II genotype (odds ratio [OR] 0.14; 95% confidence interval [CI] 0.04–0.51) and HDL cholesterol were protective for the development of HE. ACE II genotype was present in the HU group, compared with the HE group (OR 0.18; 95% CI 0.04–0.88). This study shows an association between the low prevalence of ACE I/D polymor- phism II genotype and a greater occurrence of HE in Brazilian individuals. The lower blockage of RAS, which was detected in the HE group, may interact with the low frequency of II genotype, conferring an increased risk for HE. Introduction H ypertension is a worldwide health problem that raises the costs for the public health care system. The preva- lence of hypertension in 2000 was 26.4% in the adult popu- lation and is projected to reach 29.2% in 2025 (Kearney et al., 2005). In absolute numbers, 972 million people had hyper- tension in 2000 and 1.56 billion will have high blood pressure (BP) in 2025. Inadequately controlled BP increases the risk for hypertensive crisis (HC), a condition defined as a fast, in- appropriate, intense, and symptomatic increase in BP, which is characterized by diastolic BP ‡ 120 mmHg (Chobanian et al., 2003). Hypertensive emergency (HE) is defined as HC in the presence of acute deterioration of target organs (heart, brain, kidneys, and arteries). Hypertensive urgency (HU) is characterized by the absence of acute target-organ damage (Chobanian et al., 2003). Although the description of these two conditions is well known, only a few studies compare the characteristics of individuals with HU and HE (Zampa- glione et al., 1996; Martin et al., 2004; Vilela-Martin et al., 2011). Among the possible etiological factors associated with the development of HC, some genetic factors should be em- phasized, especially the genetic polymorphisms of the renin– angiotensin system (RAS) (Sunder-Plassmann et al., 2002). An insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was previ- ously reported to be associated with different plasma ACE levels, and individuals carrying the D allele had higher ACE activities (Rigat et al., 1990). The D allele has also been 1 Internal Medicine Department, Hypertension Clinic—Hospital de Base, State Medical School of Sa ˜o Jose ´ do Rio Preto (FAMERP), Sa ˜o Paulo, Brazil. 2 Molecular Biology Department, FAMERP, Sa ˜ o Paulo, Brazil. 3 Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Queensland, Australia. 4 Cardiovascular Pharmacology Laboratory, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil. DNA AND CELL BIOLOGY Volume 32, Number 9, 2013 ª Mary Ann Liebert, Inc. Pp. 1–8 DOI: 10.1089/dna.2012.1951 1