An epidemiological study of blood pressure and metabolic phenotypes in relation to the Gbeta3 C825T polymorphism

The 825T allele of the G-protein beta(3)-subunit gene is associated with increased intracellular signalling and adipogenesis in experimental studies. We studied the C825T polymorphism in relation to blood pressure, obesity and intermediate phenotypes in a Caucasian population.

We genotyped 737 men and 775 women (participation rate, 64.3%) enrolled in a Belgian population study. Dichotomous phenotypes were tested for association with the C825T polymorphism by Fisher's exact test and multiple logistic regression. For continuous traits, we used analysis of covariance and generalized estimating equations.

The T allele (39.7 versus 29.1%) and TT genotype (16.1 versus 7.7%) were more prevalent in obese men than in non-obese men (P < or = 0.01). TT homozygous men, compared with C allele carriers, had higher daytime ambulatory blood pressure (mean systolic/diastolic differences, 3.6/2.5 mmHg; P < or = 0.02), higher body weight (2.7 kg, P = 0.04), greater risk of obesity (risk ratio, 1.90; P = 0.005), increased triceps skinfold thickness (2.3 mm, P = 0.007), higher serum insulin concentration (4.1 mU/l, P = 0.006), more insulin resistance (P = 0.01), and increased erythrocyte count (0.11 x 1012 cells/l, P = 0.04) and haematocrit (0.9%, P = 0.02). In women, haematocrit and erythrocyte count were also higher (P < or = 0.03) in T allele carriers, but other phenotypes were not correlated with the C825T polymorphism.

Male and female carriers of the T allele at position 825 of the G-protein beta(3)-subunit gene have a slightly higher haematocrit and erythrocyte count. Male TT homozygotes have a higher blood pressure and are more obese and insulin-resistant than C allele carriers. We speculate that the higher blood pressure in TT homozygous men might arise via a metabolic pathway characterized by obesity and insulin resistance as well as via increased peripheral resistance secondary to the higher haematocrit.