Role of the adducin family genes in human essential hypertension

Objective In both humans and rats, polymorphisms of the
alpha adducin (ADD1) gene are involved in renal sodium
handling, essential hypertension and some of its organ
complications. Adducin functions within cells as a
heterodimer composed of various combinations of three
subunits that are coded by three genes (ADD1, 2, 3) each
located on a different chromosome.
Design These characteristics provide the biochemical basis
for investigating epistatic interactions among these loci.
Methods We examined the three adducin gene
polymorphisms and their association with ambulatory blood
pressure (ABPM) and with plasma levels of renin activity
(PRA), endogenous ouabain (EO), in 512 newly discovered
and never-treated hypertensive patients.
Results Relative to carriers of the wild type (Gly/Gly) ADD1
gene, patients carrying the mutated Trp ADD1 allele had
higher blood pressure (systolic blood pressure (SBP)
143.2 W 1.0 versus 140.6 W 0.6 mmHg P U 0.027 and
diastolic blood pressure (DBP) 94.2 W 0.77 versus
92.3 W 0.5 mmHg, P U 0.03), lower PRA and EO, consistent
with the hypothesis of the renal sodium retaining effect of
the Trp allele. Polymorphisms in the ADD2 and ADD3 genes
taken alone were not associated with these variables.
However, the differences in SBP and DBP between the two
ADD1 genotypes were greatest in carriers of the ADD3 G
allele (around + 8 mmHg). The significance of the
interaction between ADD1 and ADD3 ranged between
P = 0.020 to P = 0.006 according to the genetic model
applied.
Conclusions The interaction of ADD1 and ADD3 gene
variants in humans is statistically associated with variation
in blood pressure, suggesting the presence of epistatic
effects among these loci.