Gene Polymorphisms of the Renin-Angiotensin System and Early Development of Hypertension

Abstract

A case-control association study was conducted to investigate a possible involvement of polymorphisms of three renin-angiotensin system genes: ACE (I/D and T-3892C), AGT (M235T and T174M), and AT1R (A1166C) in the early development of hypertension. One hundred nineteen hypertensive and 125 normotensive participants aged 18 to 40 years were selected from a broader sample representative of the general population of Croatia. The selection criteria for hypertensive cases were systolic blood pressure (BP) higher than 140 mm Hg or diastolic BP higher than 90 mm Hg and a history of hypertension according to patient interview. Among the polymorphisms investigated, only those located on the ACE gene were associated with hypertension. For ACE I/D, the odds ratio for hypertension of DD versus II homozygote individuals was 2.50 (95% confidence interval [CI] 1.19-5.25) and for ACE T-3892C, the odds ratio of CC versus TT individuals was 2.32 (95% CI 1.05-5.10). Both polymorphisms of the ACE gene were in tight linkage disequilibrium. Of the investigated risk factors for hypertension, only body mass index (BMI) showed an influence on the early development of hypertension, acting independently of the ACE polymorphism. Their additive effect gives rise to 86% of hypertensives in subjects having both the DD genotype and BMI >or=30 kg/m(2). The present study provides evidence of the association of the ACE gene polymorphisms and premature hypertension. In addition, BMI proved to be another important predictor of the disorder acting independently of the ACE gene.