Gene polymorphisms and left ventricular hypertrophy in essential hypertension

Abstract

Hypertensive heart disease results from a complex interaction between haemodynamic factors, neuro-hormonal influences and genetic determinants. In the present study we investigated the association between polymorphic forms at genes of the renin-angiotensin system and the development of left ventricular hypertrophy in a case-control study. The frequency of molecular variants was compared between a group of essential hypertensive patients (stage I-II; n=70) with ventricular involvement and a group of Caucasian healthy control subjects (n=300). After performing a careful clinical and laboratory evaluation, all the enrolled patients (mean age: 49±6 yrs) underwent a 24-h ambulatory blood pressure monitoring in order to obtain a complete blood pressure profile. Left ventricular mass and main parameters of ventricular function were assessed by M-mode/2D/doppler echocardiogram. Subjects were genotyped for M235T polymorphism at the angiotensinogen (AGT) gene, A1166C mutation in the angiotensin II type 1 receptor (AT1R) gene and I/D polymorphism at the angiotensin-converting enzyme (ACE) gene. A statistically significant association was found between allelic variants at AGT, AT1R and ACE loci and essential hypertension (p<0.05). Among cases, there was an overall frequency of 0.47 for 235T allele of the AGT gene, 0.25 for C mutant allele at the AT1R locus and 0.34 for I allele of the ACE gene. AGT and AT1R gene polymorphisms were associated with the occurrence of left ventricular hypertrophy (p<0.05). Patients with D and I alleles at ACE locus did not show significant differences in left ventricular involvement. Obtained results were in accordance with data regarding other Caucasian populations. The observed genotype and allele distribution were in equilibrium as predicted by the Hardy-Weinberg equation. Essential hypertension and related target-organ damage have a multifactorial etiology influenced by multiple genetic and environmental factors. Information on polymorphisms at genes involved in blood pressure regulation will help in identifying patients at higher risk of cardiovascular damage.