G-protein beta3 subunit 825T allele and response to dietary salt in normotensive men.
OBJECTIVE
A functional single-nucleotide variant of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3 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 Gbeta3 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 Gbeta3 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).


CONCLUSIONS
These findings do not support the hypothesis that the Gbeta3 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.
Department of Internal Medicine, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany.
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U
Schorr
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Blaschke
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Beige
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Distler
A M
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Sharma
D000328:Adult; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004039:Diet, Sodium-Restricted; D005819:Genetic Markers; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000009:adverse effects*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D005819:Genetic Markers; D012982:Sodium, Dietary; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D004247:DNA; D012964:Sodium; D020962:Heterotrimeric GTP-Binding Proteins