G-protein β3 subunit 825T allele and response to dietary salt in normotensive men

Background and aims A functional single-nucleotide variant of the gene encoding the beta 3 subunit of heterotrimeric G proteins (G beta 3 C825T), associated with enhanced G-protein activation and increased activity of the sodium-proton exchanger (NHE1), has been implicated in the development of hypertension. Given the possible involvement of NHE1 in sodium homeostasis, we tested the hypothesis that the G beta 3 825T allele determines the response of the renin-angiotensin system and blood pressure to dietary salt restriction. Methods Young normotensive men (20-30 years old, n = 193) were recruited within the framework of the Berlin Salt-Sensitivity Trial and studied on low- (20 mmol/day) and high-salt (220 mmol/day) dietary protocols. Subjects were characterized for parameters of the renin-angiotensin system and blood pressure response and genotyped for the G beta 3 C825T polymorphism. Results The genotype distribution was in Hardy-Weinberg equilibrium (CC = 90, CT = 81 and TT = 22), The responses of the renin-angiotensin system and blood pressure to the dietary protocol were virtually identical between the genotypic groups. Furthermore, when subjects were classified as salt-resistant (n = 145) or salt-sensitive (n = 48), genotype distribution was comparable between the two groups (salt-resistant: TT = 17, CT = 60, CC = 68, qT = 0.32; salt-sensitive: TT = 5, CT = 21, CC = 22, qT = 0.32). Conclusion These findings do not support the hypothesis that the G beta 3 C825T polymorphism determines the response of the renin-angiotensin system to salt depletion or can serve as an early genetic marker of salt sensitivity in young normotensive men. J Hypertens 2000, 18:855-859 (C) Lippincott Williams & Wilkins.