Low-renin hypertension, altered sodium homeostasis, and an α-adducin polymorphism

Frederick D. Grant, Jose R. Romero, Xavier Jeunemaitre, Steven C. Hunt, Paul N. Hopkins, Norman H. Hollenberg, Gordon H. Williams

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Defining the genetic basis of common forms of human essential hypertension is most informative when correlated with physiological mechanisms that underlie blood pressure regulation. A polymorphism of the alpha-adducin gene as been associated with elevated blood pressure in the rat, but previous studies of the 460Trp polymorphism of the human alpha-adducin gene have not clearly identified an association with hypertension. In this study, the frequency of the 460Trp allele was 19% and 9 of 279 subjects (3.2%) were homozygous for the 460Trp allele. The systolic blood pressure response to changes in dietary sodium was significantly greater in subjects homozygous for the 460Trp allele (25±4 mm Hg) compared with subjects heterozygous for 460Trp (12±2 mm Hg) or homozygous for the 460Gly allele (14±1 mm Hg). Intracellular erythrocyte sodium content, sodium-lithium countertransport, and renal fractional excretion of sodium were significantly decreased in subjects homozygous for the 460Trp polymorphism (P<0.05). There was a significant association between homozygosity for the 460Trp allele and low-renin hypertension. Subjects heterozygous for the 460Trp allele did not have increased salt-sensitivity or an increased frequency of low-renin hypertension. Therefore, this study demonstrates a common genetic basis for altered cellular sodium homeostasis, impaired renal sodium handling, and salt-sensitivity of systolic blood pressure in individuals homozygous for the 460Trp polymorphism of the alpha-adducin gene. Homozygosity for this alpha-adducin allele may be an important determinant for approximately 10% of individuals with low-renin hypertension.

Original languageEnglish
Pages (from-to)191-196
Number of pages6
Issue number2 I
Publication statusPublished - 4 Mar 2002


  • Genetics
  • Hypertension, essential
  • Ion transport
  • Sodium, dietary
  • Water-electrolyte balance

ASJC Scopus subject areas

  • Internal Medicine

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    Grant, F. D., Romero, J. R., Jeunemaitre, X., Hunt, S. C., Hopkins, P. N., Hollenberg, N. H., & Williams, G. H. (2002). Low-renin hypertension, altered sodium homeostasis, and an α-adducin polymorphism. Hypertension, 39(2 I), 191-196. https://doi.org/10.1161/hy0202.104273