(Hypertension. 2002;39:191.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Low-Renin Hypertension, Altered Sodium Homeostasis, and an 
-Adducin Polymorphism
From the Endocrinology-Hypertension Division, Department of Medicine, Brigham and Women’s Hospital (F.D.G., J.R.R., G.H.W.), Harvard Medical School, Boston, Massachusetts; Centre d’Investigation Clinique, Hopital Broussais and INSERM U36 College de France (X.J.), Paris, France; Cardiovascular Genetics Research Unit, Department of Medicine, University of Utah School of Medicine (S.C.H., P.N.H.), Salt Lake City, Utah; and Department of Radiology, Brigham and Women’s Hospital (N.H.H.), Harvard Medical School, Boston, Massachusetts.
Correspondence to Frederick D. Grant, MD, Endocrinology-Hypertension Division, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115. E-mail frederick.grant{at}tch.harvard.edu
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.
Key Words: hypertension, essential • genetics • sodium, dietary • water-electrolyte balance • ion transport
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