(Hypertension. 1999;34:649-654.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
The Role of 
-Adducin Polymorphism in Blood Pressure and Sodium Handling Regulation May Not Be Excluded by a Negative Association Study
From Clinica Medica (N.G., F.F., C.T., A.S., F.D., P.P.P.), University of Sassari Medical School, Sassari, Italy; and the Chair of Nephrology, University of Milano, Division of Nephrology, Dialysis and Hypertension (P.M., P.S., C.B., C.L., M.T.S.A., D.C., G.B.), San Raffaele Hospital, IRCCS, Milano, Italy.
Correspondence to Nicola Glorioso, MD, Clinica Medica, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy. E-mail glorioso{at}ssmain.uniss.it
Abstract—The basic requirement
for declaring an association study positive is that the
"hypertension-favoring" allele is more frequent in hypertensive
cases than in normotensive controls. However, both positive and
negative associations with hypertension have been found for the same
polymorphism when studied in different populations. In the
present study, we addressed the question of the possible cause(s)
of this discrepancy among populations by using the 
-adducin
polymorphism as a paradigm. Four hundred ninety hypertensives and
176 normotensives enrolled in Sassari, Italy, and 468 hypertensives and
181 normotensives enrolled in Milano, Italy, were genotyped for
the -adducin Gly460Trp polymorphism. The blood pressure response
to 2 months of hydrochlorothiazide therapy could be
evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with
and without the 460Trp -adducin allele. The -adducin 460Trp
allele was not significantly more frequent in hypertensives in the
Sassari population but was more frequent in hypertensives than in
normotensives in Milano (P=0.019). Basal plasma renin
activity was lower and blood pressure fall after diuretic
therapy more pronounced (P<0.01) in hypertensives
carrying at least one 460Trp allele than in Gly460Gly homozygotes,
irrespective of their membership in the Sassari or Milano cohort. The
effect of -adducin genotype in predicting basal plasma renin
activity and blood pressure decrease with diuretic treatment is
similar in Sassari and Milano, despite the lack of association of the
-adducin genotype with hypertension in Sassari.
Key Words: genes • hypertension, genetic • sodium • renin • adducin
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