Pharmacogenomics and pharmacogenetics of hypertension: Update and perspectives - The adducin paradigm

Paolo Manunta, Giuseppe Bianchi

Research output: Contribution to journalArticle

Abstract

There is a growing literature on the potential prospective use of genome information to enhance success in finding new medicines. An example of a prospective efficacy of pharmacogenetic and pharmacogenomics is the detection and impact of adducin polymorphism on hypertension. Adducin is a heterodimeric cytoskeleton protein, the three subunits of which are encoded by genes (ADD1, ADD2, and ADD3) that map to three different chromosomes. A long series of parallel studies in the Milan hypertensive rat strain model of hypertension and humans indicated that an altered adducin function might cause hypertension through an enhanced constitutive tubular sodium reabsorption. In particular, six linkage studies, 18 of 20 association studies, and four of five follow-up studies that measured organ damage in hypertensive patients support the clinical impact of adducing polymorphism. As many modulatory genes and environment affect the adducin activity, the context must be taken into account to measure the clinical effect size of adducins. Pharmacogenomics is giving an important contribution to this end. In particular, the selective advantages of diuretics in preventing myocardial infarction and stroke over other antihypertensive therapies that produce a similar BP reduction in carriers of the mutated adducin may support new strategies that aim to optimize the use of antihypertensive agents for the prevention of hypertension-associated organ damage.

Original languageEnglish
JournalJournal of the American Society of Nephrology
Volume17
Issue numberSUPPL. 2
DOIs
Publication statusPublished - Apr 2006

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Pharmacogenetics
Hypertension
Antihypertensive Agents
Protein Subunits
Cytoskeleton
Diuretics
Genes
adducin
Chromosomes
Sodium
Stroke
Myocardial Infarction
Genome

ASJC Scopus subject areas

  • Nephrology

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Pharmacogenomics and pharmacogenetics of hypertension : Update and perspectives - The adducin paradigm. / Manunta, Paolo; Bianchi, Giuseppe.

In: Journal of the American Society of Nephrology, Vol. 17, No. SUPPL. 2, 04.2006.

Research output: Contribution to journalArticle

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