ASSOCIATION BETWEEN A POLYMORPHISM IN THE G-PROTEIN BETA-3 SUBUNIT GENE AND LOWER RENIN AND ELEVATED DIASTOLIC BLOOD-PRESSURE LEVELS

G(i) proteins mediate the intracellular effects of many vasoactive and proliferative stimuli. Recently such signaling was found to be enhanc ed in cultured cells of some hypertensive subjects. A polymorphism at position 825 (C-->T) of the G protein beta 3 subunit gene (GNB3) was s trictly related to this phenotype. The aim of the present investigatio n was to test the association between this polymorphism and blood pres sure and plasma renin levels in humans. A population-based sample (n=6 08) was analyzed by questionnaire and characterized for blood pressure ; plasma renin, prorenin, and aldosterone levels; and G(beta 3) C825T allele status. In individuals without antihypertensive medication (n=4 74; age range, 52 to 67 years), the polymorphism was mildly associated with diastolic blood pressure (CC: 88.6+/-0.3 mm Hg, n=218; versus CT : 90.1+/-0.7 mm Hg, n=209; versus TT: 91.8+/-1.7 mm Hg, n=47; P=0.02 f or trend) but not with systolic blood pressure. Furthermore, the 825T allele was also significantly associated with lower renin and prorenin levels, whereas the aldosterone to renin ratio was elevated in these subjects. Significant associations between the 825T allele and diastol ic blood pressure, plasma renin, and prorenin levels (inverse), and th e aldosterone to renin ratio persisted after adjustment for age, gende r, body mass index, and systolic blood pressure, Finally, when the ent ire sample was considered and an adjustment was made for covariates, t he presence of arterial hypertension and the use of antihypertensive m edication were both 1.8-fold higher in the TT than in the CC genotype group (P<0.05 and P=0.06, respectively). This observation, if replicat ed in further studies; suggests a molecular mechanism that unifies a h igher diastolic blood pressure, a lower renin level, and an elevated a ldosterone to renin ratio, ie, a combination of features frequently fo und in patients with arterial hypertension.