G-protein β3 subunit C825T polymorphism and salt sensitivity in essential hypertension

The genetic functional variant C for T in position 825 of the gene encoding G protein beta (3) subunit, GNB3, has been associated with enhanced G protein activation, cell growth and proliferation. This phenotype is associated with enhanced G protein activation and Na+-H+ exchanger activity in cells from hypertensive patients. Salt sensitivity affects approximately 50% of hypertensive patients and constitutes an intermediate phenotype determined in part by genetic factors. An association between enhanced Na+-H+ exchanger activity and salt sensitivity has been previously reported. The aim of the present study was to investigate the possible association between the G protein polymorphism and salt sensitivity in patients with essential hypertension. A total of 46 patients were studied and classified according to their blood pressure response to a change in sodium intake from low (20 mmol/day) to high (260 mmol/day) into salt sensitive (SS) (n=20) and salt resistant (SR) (n=26). GNB3 polymorphism was determined by PCR of genomic DNA and restriction digestion with BseDI. The genotypes distribution among the SS hypertensives was: 8 CC and 12 CT + TT, whereas in SR was: 10 CC and 16 CT + TT (p=0,577). 24 h mean blood pressure response to salt in the whole group was not different among the different genotypes: CC 4.1 +/-5.4 mmHg compared to CT + TT 2.9 +/-6.3 mmHg (p=0.51). There were no significant differences in the salt induced changes in plasma renin activity, aldosterone, ANP or noradrenaline among the different genotypes. These results indicate that the GNB3 C825T polymorphism has no major influence on the pressor response to salt in essential hypertension and therefore do not support its usefulness as an early genetic marker of salt sensitivity in this disease.