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The Role of α-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study

Glorioso, Nicola and Manunta, Paolo and Filigheddu, Fabiana and Troffa, Chiara and Stella, Paola and Barlassina, Cristina and Lombardi, Cinzia and Soro, Aldo and Dettori, Francesco and Pinna Parpaglia, Paolo and Sciarrone Alibrandi, Maria Teresa and Cusi, Daniele and Bianchi, Giuseppe (1999) The Role of α-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study. Hypertension, Vol. 34 (4), p. 649-654. eISSN 1524-4563. Article.

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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 α-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 α-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 α-adducin allele. The α-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 α-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 α-adducin genotype with hypertension in Sassari.

Item Type:Article
ID Code:785
Status:Published
Refereed:Yes
Uncontrolled Keywords:Genes, hypertension, genetic, sodium, renin, adducin
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
Publisher:Lippincott Williams & Wilkins
eISSN:1524-4563
Copyright Holders:© 1999 American Heart Association
Deposited On:18 Aug 2009 10:03

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