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(Hypertension. 1999;33:694-697.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Adducin Polymorphism Affects Renal Proximal Tubule Reabsorption in Hypertension

Paolo Manunta; Michel Burnier; Marco D'Amico; Laura Buzzi; Marc Maillard; Cristina Barlassina; Giovanna Lanella; Daniele Cusi; Giuseppe Bianchi

Correspondence and reprint requests to Paolo Manunta, MD, Chair of Nephrology, University of Milan, Division of Nephrology Dialysis and Hypertension, S. Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy. E-mail manunta.paolo{at}hsr.it

Abstract—Abnormalities in renal sodium reabsorption may be involved in the development and maintenance of experimental and clinical hypertension. Adducin polymorphism is thought to regulate ion transport in the renal tubule. It has recently been shown that there is a significant linkage of -adducin locus to essential hypertension and that the 460Trp allele is associated with hypertension. Patients with this allele display larger blood pressure changes with body sodium variation. The aim of this study was to test whether -adducin polymorphism is involved in abnormalities of renal function. Because proximal tubular reabsorption has been shown to be tightly coupled to renal perfusion pressure, this segmental tubular function was investigated in 54 (29 Gly/Gly and 25 Gly/Trp) untreated hypertensive patients in basal conditions with the use of endogenous lithium concentration and uric acid. Fractional excretions of lithium and uric acid were significantly decreased in the Gly/Trp hypertensive patients compared with the Gly/Gly hypertensives. The contribution of -adducin to fractional excretion of lithium was investigated by multiple regression analysis. Adducin genotype was significantly (R²=0.11, F=6.5; P<0.01) and directly related to fraction excretion of lithium; gender, age, urinary Na⁺, urinary uric acid, mean blood pressure, and plasma renin activity were not related. In conclusion, the adducin gene can be considered to be a `renal hypertensive gene' that modulates the capacity of tubular epithelial cells to transport Na⁺ and hence contributes to the level of blood pressure.

Key Words: lithium • genes • human • renal function • blood pressure • adducin • hypertension, genetic

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