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Il Gene del cotrasportatore NaCl tiazide-sensibile è associato con l'attività reninica plasmatica e l'effetto antiipertensivo dei diuretici tiaridici nell'ipertensione arteriosa essenziale

Pitzoi, Silvia (2009) Il Gene del cotrasportatore NaCl tiazide-sensibile è associato con l'attività reninica plasmatica e l'effetto antiipertensivo dei diuretici tiaridici nell'ipertensione arteriosa essenziale. Doctoral Thesis.

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Abstract

Essential hypertension originates from gene-environment interaction. Thiazide diuretics play a key role in the treatment of essential hypertension. Several gene polymorphisms have been inconclusively associated with the antihypertensive effect of thiazides because of:
1. small sample size>
2. evaluation of patients with short wash-out period from previous therapy
3. genetic heterogeneity
4. no intermediate phenotypes
5. uncertainties in gene interactions
In a cohort of genetically homogeneous, never treated essential hypertensives we analyzed the association of the “Thiazide Sensitive Channel” gene with 1. the effect of hydrochlorothiazide on blood pressure, and 2. coherent intermediate phenotypes, by means of Linkage Disequilibrium analysis [Single Nucleotide Polymorphisms (SNPs) inside “haplotype blocks”]. Several SNPs in different haplotype blocks are associated with indexes of "volume status" while other SNPs are associated with the effect of hydrochlorothiazide on blood pressure. No association with pre-treatment blood pressure was found. Our study confirms that 1. different polymorphisms inside the same gene may regulate different phenotypic expression, and 2. blood pressure regulation and the antihypertensive effect of drugs may be regulated by independent genetic mechanisms.

Item Type:Doctoral Thesis
ID Code:1014
Publisher:Universita' degli studi di Sassari
Uncontrolled Keywords:Farmacogenomica, antiipertensivi, pressione arteriosa, PRA, aplotipi
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Patologia speciale medica e metodologia clinica
Cicli, scuole e corsi:Ciclo 21 > Corsi > Fisiopatologia medica
Deposited On:18 Aug 2009 10:04

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