CAROTID INTIMA-MEDIA THICKNESS IN RELATION TO GENETIC VARIATION IN RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN PROSPECTIVE OBSERVATION: PP.35.450

Abstract

Objective: The essential role of the renin-angiotensin-aldosterone system (RAAS) in controlling blood pressure has been well established. Genes encoding components of the RAAS have been proposed as candidate genes that determine genetic predisposition to hypertension and the risk of developing cardiovascular complications. The aim of the study was to evaluate follow-up changes in carotid intima-media thickness (IMT) in relation to genetic polymorphisms in 5 genes of the RAAS: angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT, A-6G), aldosterone synthase (CYP11B2, T-344C), angiotensin II receptors type 1 (ATR1, A1166C) and type 2 (ATR2, G1675A). Design and Methods: We examined 147 subjects, members of 45 nuclear families, enrolled in the population-based study in Krakow. The subjects underwent at baseline and on follow-up (6.4+/−0.5 yrs) conventional BP measurement during two separate visits, 5 times on each visit. Anthropometric data were collected with standardized protocol. Peripheral blood was sampled for genotyping. Carotid IMT was measured by carotid ultrasound (Hewlett Packard Sonos 2000 - baseline and VIVID 7 GE Pro - follow-up). In our analyses, we adjusted for covariables and non-independence among related subjects. Results: The study group included 71 M/76F, at baseline mean age was 37.6+/−14.2 yrs, BMI 26.0+/−5.2 kg/m2, BP 128.1+/−17.6/80.0+/−11.2 mmHg. In multivariate analyses, the change in IMT on follow-up was significantly associated with ACE I/D polymorphism (p = 0.008). The ACE II homozygotes showed higher increase in IMT as compared to D-allele carriers (change in IMT 0.252+/−0.043 vs. 0.093+/−0.022 mm, p = 0.002). The results were consistent among male and female, and among parents and offspring. The genetic polymorphisms in CYP11B2, AGT, ATR1 or ATR2 did not associate with phenotype under study. Conclusion: Insertion/deletion (I/D) polymorphism of the ACE gene associates with prospective increase in carotid intima-media thickness. However, the present findings need further confirmation in a larger/multicentre cohort.