A common polymorphism in the renin angiotensin system is associated with differential outcome of antihypertensive pharmacotherapy prescribed to Brazilian older women Clayton F. Moraes a,c , Elias R. Souza a , Vinícius C. Souza a , Eloá F.F. Medeiros a , Thiago F. Gonçalves a , Juliana O. Toledo a , Mauro Karnikowski a , Lucy Gomes a , Margô G.O. Karnikowski a , Cláudio Córdova b , Otávio T. Nóbrega a, ⁎ a Postgraduation Program Stricto Sensu in Gerontology, Catholic University of Brasília (UCB), Q.S. 07, Lote 01, EPCT, Águas Claras, CEP 72030-170 Brasília-DF, Brazil b Postgraduation Program Stricto Sensu in Physical Education, Catholic University of Brasília, Brasília-DF, Brazil c Geriatrics Service, Hospital of the Catholic University of Brasília, Brasília-DF, Brazil ABSTRACT ARTICLE INFO Article history: Received 17 April 2008 Received in revised form 23 June 2008 Accepted 2 July 2008 Available online 6 July 2008 Keywords: Renin angiotensin system Polymorphism Hypertension Pharmacotherapy Guidelines Brazil Background: Since variations on the renin angiotensin (RA) system tend to exert effects on blood pressure, we investigated the association of the common ACE and AT 1 R polymorphisms with response to a multivariate pharmacotherapy. Methods: This prospective study involved 169 hypertensive, community-dwelling older women. Genotypes were obtained by length analysis or direct sequencing of PCR products. Blood pressure-lowering pharmacotherapy was conducted according to current Brazilian Guidelines on Hypertension. Results: Genotype frequencies were in agreement to the Hardy–Weinberg equilibrium. Interventions were found to represent actual hypertension-management practices in Brazil, and accounted for a significant reduction in both systolic (P b 0.001) and diastolic (P b 0.001) blood pressure. Concerning the effect of polymorphisms, no influence of the ACE and AT 1 R genotypes were found on the magnitude of the treatment- induced blood pressure reduction (P N 0.05). Nonetheless, the clinical result varied according to the ACE alleles since mean systolic pressure was roughly 10 mm Hg higher in insertion (I) homozygotes than in the deletion (D) counterparts either in baseline (P = 0.001) and endpoint (P = 0.010). Conclusion: The outcome of the antihypertensive pharmacotherapy advocated by national guidelines was significantly influenced by the ACE I/D polymorphism but not by the AT 1 R 1166 A/C polymorphism among postmenopausal women. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Hypertension is a common disorder affecting nearly 972 million people worldwide, being 639 million in economically developing countries [1]. In Brazil, estimates from the Health Ministry indicate that N 25 million people bear this disorder among adults ≥ 25 years, of whom 8 million are ≥ 60 years [2]. There is substantial evidence establishing the augmented morbidity and mortality associated with hypertension, and the benefits of blood pressure (BP) lowering treatments in reducing that risk [3]. Despite the clinical and public health burden that accompanies hypertension, bringing down BP in hypertensive patients to low risk levels is hardly achieved in Brazil. Despite age-related problems, other factors that refrain an effective antihypertensive treatment are those related to shortcomings in the Brazilian health system, with emphasis to the unequal access to specialized medical advice to the aged [4], unavailability of pharmaceutical goods through the public system [5], elevated retail prices in private pharmacies [6] and poor pharmaceutical care to optimize drug use and prevent drug-related problems [7,8]. On top of these major aspects closely related to public health policies, another challenge in achieving successful control of BP consists in predicting the efficacy and the risks of any broad therapeutic strategy in a heterogeneous population. Physicians often use the trial-and-error approach to find the optimum drug for a given patient, and clinical attempts usually benefit from a certain combination of drugs and posologic directions, especially for the aged [9]. For that purpose, a cast of possible pharmaceutical products (e.g., diuretics, β-blockers and renin angiotensin system drugs, among others) and administration directions are indicated in the so-called Brazilian Guidelines on Hypertension [10]. Nonetheless, and as a point of caution, pharmacogenetic studies are usually designed to draw conclusion from a completely standardized Clinica Chimica Acta 396 (2008) 70–75 ⁎ Corresponding author. Programa de Pós-Graduação Stricto Sensu em Gerontologia, Universidade Católica de Brasília, Q.S. 07, Lote 01, EPCT, Águas Claras, Building B, room 105, Taguatinga (DF), CEP 72030-170, Brazil. Tel.: +55 61 3356 9693, +55 6184513718 (mobile); fax: +55 61 3356 3010. E-mail address: nobrega@pq.cnpq.br (O.T. Nóbrega). 0009-8981/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2008.07.002 Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim