Adducin polymorphism affects renal proximal tubule reabsorption in hypertension

Abnormalities in renal sodium reabsorption may be involved in the developme nt and maintenance of experimental and clinical hypertension Adducin polymo rphism is thought to regulate ion transport in the renal tubule. It has rec ently been shown that there is a significant linkage of alpha-adducin locus to essential hypertension and that the 460Trp allele is associated with hy pertension. Patients with this allele display larger blood pressure changes with body sodium variation. The aim of this study was to test whether alph a-adducin polymorphism is involved in abnormalities of renal function. Beca use proximal tubular reabsorption has been shown to be tightly coupled to r enal perfusion pressure, this segmental tubular function was investigated i n 54 (29 Gly/Gly and 25 Gly/Trp) untreated hypertensive patients in basal c onditions with the use of endogenous lithium concentration and uric acid. F ractional excretions of lithium and uric acid were significantly decreased in the Gly/Trp hypertensive patients compared with the Gly/Gly hypertensive s. The contribution of alpha-adducin to fractional excretion of lithium was investigated by multiple regression analysis. Adducin genotype was signifi cantly (R-2 = 0.11, F = 6.5; P < 0.01) and directly related to fraction exc retion of lithium; gender, age, urinary Na+, urinary uric acid, mean blood pressure, and plasma renin activity were not related. Ln conclusion, the ad ducin gene can be considered to be a 'renal hypertensive gene' that modulat es the capacity of tubular epithelial cells to transport Na+ and hence cont ributes to the level of blood pressure.