Abstract 4436: Direct Relation between Angiotensin-Converting Enzyme (ACE) Gene Polymorphisms and Hypertension in Patients with Stable Coronary Artery Disease
Background: The Angiotensin-Converting Enzyme (ACE) plays an essential role in the blood-pressure regulation by the renin-angiotensin-system and has become an important antihypertensive drug target.
Objective: To investigate whether genetic polymorphisms in the ACE gene are related to hypertension.
Methods: Hypertension was defined by study protocol as 160/95 mmHg or the use of antihypertensives. DNA was available in 10060 Caucasian patients with stable coronary artery disease. Six polymorphisms in the ACE gene were genotyped based on functionality, location (promotor) or literature search. The Taqman allelic discrimination was used to determine all genotypes. Genotype information was available in 9466 subjects (95%). In multivariate logistic regression analysis we adjusted for age, gender, hypercholesterolemia, diabetes, prior MI, prior PCI, prior CABG, use of statins, beta-blockers, platelet- and ACE-inhibitors.
Results: Mean age was 60 (Sd 9) years, and 85.7% were male. Minor allele frequencies (MAF) ranged from 39 – 48% (figure 1). Results of the multivariate analysis are presented in figure 1 (reference category 1/1 normal alleles). Several minor alleles of polymorphisms in the ACE gene, especially those located in the promotor region, identified a 24% significant increased prevalence of hypertension.
Conclusions: Genetic polymorphisms in the ACE gene are directly and independently associated with hypertension in patients with stable coronary artery disease. Sponsored by grants from the NHS-B219) and the Netherlands Organisation for Health Research and Development (Dr. Brugts ZonMW).