Low-renin hypertension, altered sodium homeostasis, and an alpha-adducin polymorphism.
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.
Grant
Frederick D
FD
Endocrinology-Hypertension Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. frederick.grant@tch.harvard.edu
Romero
Jose R
JR
Jeunemaitre
Xavier
X
Hunt
Steven C
SC
Hopkins
Paul N
PN
Hollenberg
Norman H
NH
Williams
Gordon H
GH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000097:blood*; D012982:Sodium, Dietary / Q000008:administration & dosage; D000099291:Adducins
D001786:Blood Glucose; D002148:Calmodulin-Binding Proteins; D006854:Hydrocortisone; D007328:Insulin; D011188:Potassium; D012083:Renin; D012964:Sodium; D012982:Sodium, Dietary; D000099291:Adducins