Renin-angiotensin-aldosterone system and G-protein beta-3 subunit gene polymorphisms in salt-sensitive essential hypertension

Abstract

Approximately 50% of hypertensive patients are salt sensitive (they increase their Blood Pressure in response to sodium intake or volume expansion). Mechanisms underlying salt sensitivity are not completely elucidated although there is evidence that they may be genetically determined. The aim of this study is to establish the relation among some genetic polymorphisms of the renin-angiotensin system (RAAS) and the beta-3 subunit of the protein G and salt sensitivity. We studied 102 essential hypertensive patients, stage 1-2 and without target organ damage. Salt sensitivity was assessed by the rapid protocol of Weinberger. We determined by polymerase Chain reaction techniques the following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme (ACE), A1166C of the angiotensin II type 1 receptor (AT1R), -344C/T and intron 2 conversion (IC) of the aldosterone synthase (CYP11B2), and C825T of the beta-3 subunit of the protein G (GNB3). 41 patients (40.19%) were salt sensitive. The distribution of the different polymorphisms was similar in both groups of patients, but subjects carriers of the W allele of the CYP11B2 IC polymorphism had a greater risk for salt sensitivity as compared with no carriers (37 of 41, 90.2% vs 4 of 41, 9.8%, OR 3.02, P<0.05). Although there is no association between salt sensitivity and the different studied genotypes of the RAAS and of the GNB3, our data show a greater risk for salt sensitivity among carriers of the W allele of the CYP11B2 1C polymorphism.

Polymorphisms ofEDNRB,ATG, andACEgenes in salt-sensitive hypertensionThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

“…The role of polymorphisms of both AGT M235T (Beeks et al 2004;Schorr et al 1999;Hunt et al 1999) and ACE I/D (Beeks et al 2004;Pamies-Andreu et al 2003;Dengel et al 2001) in salt-sensitive hypertension is controversial, although well-established evidence exists as to their role in hypertension, diabetic and nondiabetic nephropathy, and cardiovascular diseases (Cambien et al 1992;Schunkert et al 1994). In the present study, a statistically significant association was found for the TT genotype in hypertensive patients, as expected.…”

Genetics of salt-sensitive hypertension

“…Studies exploring its possible association with salt sensitivity and susceptibility to hypertension gave contrasting results [34][35][36]. In a recent study, Martin et al [37] found no association between this polymorphism and SSBP or prevalence of hypertension; nevertheless, they observed that plasma sodium concentration was higher and plasma potassium was lower in TT than in CC patients, a finding suggesting that increased NHE-1 activity is associated with the less common allelic variant of the gene.…”

Association of AT1R polymorphism with hypertension risk: An update meta-analysis based on 28,952 subjects

“…There were 39 studies carried out in Asian populations, [19][20][21][22]57,58,61,63,65 while 15 studies were performed in Caucasian populations. [11][12][13]18,23,[54][55][56]59,60,62,64,[66][67][68] Only two studies involved an African population. 17,18 …”