1. ¹Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy
2. ²Institut für Pharmakologie, Universitätsklinikum Essen, Essen, Germany
3. ³Abteilung für Kardiologie, Universitätsklinikum Essen, Essen, Germany
4. ⁴Medicina Generale, Vittorio Veneto Town Hospital, Vittorio VenetoItaly
5. ⁵Mayo Clinic, Rochester, Minnesota, USA

Correspondence: Prof. Andrea Semplicini, Clinica Medica 4, Policlinico Universitario, via Giustiniani 2, 35126 Padova, Italy. E-mail: andrea.semplicini@unipd.it

^*This study was partially supported by the Regione Veneto grant 782/01/97 to AS, a scholarship grant of the Italian Society of Hypertension to MS, and through a grant of the Deutsche Forschungsgemeinschaft to WS.

Received 6 April 2001; Accepted 29 June 2001.

Abstract

Background: A nucleotide substitution (CT) at position 825 of the gene GNB3 encoding the ₃ subunit of heterotrimeric G proteins is associated with alternative splicing and enhanced signal transduction. There is accumulating evidence from different populations that the 825T allele is associated with increased prevalence of hypertension, obesity, and left ventricular hypertrophy. However, it is unclear to what extent the 825T allele has a direct influence on left ventricular structure, independently of the effects of pressure and body mass index. Therefore we explored whether the GNB3 825T allele is associated with increased left ventricular mass index in a selected and homogeneous group of young, never treated, mild hypertensives.

Procedures: Young subjects (n = 207, aged 18 to 45 years) were genotyped at the GNB3 825 locus. In each patient, 24-h ambulatory blood pressure (BP) measurement and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed.

Results: The genotype distribution among patients was in Hardy-Weinberg equilibrium. Patients carrying the 825T allele had an increased left ventricular mass index (95.1 1.5 v 89.7 1.5 g/m²; P = .01) in comparison to those with CC genotype. The association between left ventricular mass index and 825T allele was independent of gender, age, BP, heart rate, alcohol intake, and physical activity.

Conclusions: In young patients with mild hypertension without heart disease the 825T allele is associated with an increased left ventricular mass index. These hypothesis-generating data suggest that GNB3 825T allele may be considered as one genetic marker predisposing to an increase in left ventricular mass in hypertensives, and justifies larger studies.