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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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
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.
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