Alpha-adducin polymorphism, salt sensitivity, nitric oxide excretion, and cardiovascular risk factors in normotensive Hispanics.
BACKGROUND
Genetic and environmental factors determine the blood pressure (BP) response to changes in salt intake. Mutations in the alpha-adducin gene may be associated with hypertension and salt-sensitive hypertension. We investigated whether one alpha-adducin polymorphism, the Gly460Trp (G/T) variant, was associated with salt sensitivity, nitric oxide (NO) production; and cardiovascular risk factors in healthy adult normotensive Venezuelans.


RESULTS
Subjects (n = 126) were screened for salt sensitivity. The alpha-Adducin polymorphism was tested in salt-sensitive (SS) and salt-resistant (SR) subjects. The G/T and G/G (wild gene) groups had similar BP levels. The G/T subjects had higher LDL-cholesterol (P =.01) and postload glucose AUC (P =.03) than G/G individuals. Genotype frequencies were not associated with BP or salt sensitivity (G/G, 38.1% SS and 61.9% SR vs G/T, 40.7% SS and 59.3% SR). Shifting from high salt to low salt diet produced comparable reductions in systolic BP and diastolic BP in G/T and G/G groups. The G/G and G/T groups excreted similar amounts of sodium on high and low salt diets. The SR subjects carrying the wild or the mutated gene showed no changes in NO metabolite excretion at different levels of salt intake. In SS subjects, the level of NO metabolite excretion was highly dependent on salt intake. A combination of SS and 460Trp mutation enhanced the sodium-dependent modulation of NO production.


CONCLUSIONS
In normotensive Venezuelans, the alpha-adducin G/T polymorphism was not associated with BP, salt sensitivity, or with sodium excretion during sodium loading or restriction. G/T was associated with increased LDL-cholesterol and postload glucose levels. In SS, G/T was associated with greater salt-dependent modulation of NO excretion. However, this larger increase in NO excretion was not associated with a larger decrease in BP.
Castejon
Ana M
AM
Department of Pharmaceutical Sciences, College of Pharmacy, Health Professions Division, NOVA Southeastern University, Fort Lauderdale, Florida 33328, USA.
Alfieri
Anna B
AB
Hoffmann
Irene S
IS
Rathinavelu
Abbu
A
Cubeddu
Luigi X
LX
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000209:etiology*; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D014687:Venezuela; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D009569:Nitric Oxide; D017673:Sodium Chloride, Dietary; D000099291:Adducins