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Genetic polymorphisms of the ß-adrenergic system: association with essential hypertension and response to ß-blockade

Filigheddu, Fabiana and Reid, Julia E. and Troffa, Chiara and Pinna Parpaglia, Paolo and Argiolas, Giuseppe and Testa, Alessandra and Skolnick, Mark H. and Glorioso, Nicola (2004) Genetic polymorphisms of the ß-adrenergic system: association with essential hypertension and response to ß-blockade. The Pharmacogenomics Journal, Vol. 4 , p. 154-160. ISSN 1470-269X. eISSN 1473-1150. Article.

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DOI: 10.1038/sj.tpj.6500247

Abstract

Essential hypertension (EH) is a polygenic, multifactorial disease. A number of genes and environmental factors must be taken into account to dissect the complexity of EH, as well as drug response.
Beta adrenergic receptors (ßARs) are G-protein-coupled receptors expressed throughout the body, involved in several pathophysiological functions such as blood pressure (BP). Genetic polymorphisms of the ßARs or of their G proteins could lead to functionally different products, higher/lower BP values or greater/smaller BP fall after ß-blockade.
ß1, ß2 and ß3 ARs polymorphisms (R389Gß1AR, R16Gß2AR and W64Rß3AR) have been associated contradictorily with EH, and R16Gß2AR was found not predictive of the antihypertensive response to ß-blockers. On the contrary, recent data have reported a greater BP fall in the R389Rß1AR carriers. The role of the G-protein α-(GNAS) and ß-(GNB3) subunit polymorphisms (T-C, Ile131GNAS and C825TGNB3) has been analyzed in EH and in the response to bblockers and thiazides, respectively. All these studies were usually conducted in limited cohorts of genetically heterogeneous patients and the response to drug evaluated after short wash-out from previous treatment.
The aim of the present study was (1) to investigate the association of known polymorphisms of ß1ARs, ß2ARs, ß3ARs, GNB3 and GNAS with EH in a cohort of genetically homogeneous EH patients and normotensive controls (case–control study) and (2) to analyze the BP fall after 4 and 8 weeks of therapy with ß-blockers according to genotype (pharmacogenetic study) in essential hypertensive patients never treated or untreated for at least 6 months.

Item Type:Article
ID Code:10761
Status:Published
Refereed:Yes
Uncontrolled Keywords:Essential hypertension (EH), beta adrenergic receptors (ßARs), genetic polymorphisms
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL1, Sassari > Centro prevenzione, diagnosi e terapia dell'ipertensione arteriosa e delle complicanze cardiovascolari
Publisher:Nature Publishing Group
ISSN:1470-269X
eISSN:1473-1150
Deposited On:05 Feb 2015 12:46

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