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

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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
JournalHypertension
Volume39
Issue number2 I
DOIs
Publication statusPublished - 4 Mar 2002

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Low-renin hypertension, altered sodium homeostasis, and an α-adducin polymorphism'. Together they form a unique fingerprint.

  • Cite this

    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