Interaction of Mutations M235T of the Gene for Angiotensinogen and Taq I8,000 in the Gene for Endothelin-1 at the Onset of Essential Hypertension

Overview

Background.
Identification of mutations contributing to the pathogenesis of essential hypertension performs tounderstand deeper consequences of developing pathophysiological changes, to value individual risk of hypertensionin the preclinical stages and, regarding the observed genotype, to choose optimum therapy. The aim of the study wasto prove the existence of difference in double genotype occurrence of polymorphic candidate genes betweennormotensive and hypertensive subjects.Methods and Results. A sample of Czech population (398 individuals), 192 normotensives (age of 45.87±3.0,BMI=25.44±3.31 kg.m-2) a 206 hypertensives (age of 48.71±8.42, BMI=27.18±4.16 kg.m-2) was genotyped atangiotensinogen (AGT, M235T polymorphism, exon 2) and endothelin-1 (EDN-1, Taq I 8000 polymorphism, intron4) genes by PCR methods. Experimental schedule was case-control. c2and Fisher-exact test were used for statisticalanalyses. M-allele of angiotensinogen gene was associated with essential hypertension (p=0.0111). Allele (-) aloneat endothelin-1 gene was associated with essential hypertension with marginal significance (p=0.0622). A significantloss of heterozygotes MT (M235 AGT) at homozygote (--) at endothelin-1 gene (p=0.0025) as well as a significantincrease of allele (-) of endothelin-1 gene at homozygote MM at angiotensinogen gene (p=0.0034) were found.Conclusions. Interaction of two polymorphic genetic variants of angiotensinogen and endothelin-1 genes wasfound. From the pathophysiological point of view, the fact may be explained as a stream to compensate the influenceof variability of other genes more causatively conditioning essential hypertension.

Key words:
24-h blood pressure monitoring, gene polymorphism, angiotensinogen (AGT), endothelin-1 (EDN-1),