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Genetic variants involved in Blood Pressure response to hydrochlorothiazide identified by GWAS methodology

Piras, Daniela Antonella (2016) Genetic variants involved in Blood Pressure response to hydrochlorothiazide identified by GWAS methodology. Doctoral Thesis.

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Abstract

Aim: To identify new loci regulating blood pressure response to thiazide diuretics (HCTZ) with a genome wide association analysis, thus optimizing therapeutic advantages and minimizing side effects.
Methods: Treatment started after a 8 week run-in period under standardized dietary regimen to qualify patients as “essential hypertensives”. Never treated mild-to-moderate hypertensive patients were studied in two Italian cohorts: n=343 patients in Sardinia and 142 in Milano. A genome-wide association study and imputation were performed: variants associated with blood pressure response to HCTZ over an 8-weeks follow up period were analysed. The specificity of our findings was confirmed in an independent cohort of never treated essential hypertensives treated with Losartan.
Results: We identified 141 SNPs and 130 SNPs showing a significant association with for deltaSBP8 for deltaDBP8 (P≤10-5). Six SNPs showed the best association with deltaSBP8 and five SNPs with deltaDBP8, respectively. TET2 and CSMD1 gene variants showed the best effect on deltaSBP after 8 weeks of HCTZ treatment. No association was found in Losartan sample. We looked for replication in other studies (GENRES, GERA1, NORDIL, PEAR and CSN-StayOnDiur).
Conclusions: TET2 and CSMD1 affect SBP response to HCTZ. TET2, may affect the transcription of αENaC gene thus acting as an aldosterone-responsive mediator. CSMD1 gene was associated with increased risk of hypertension: its putative role in BP regulation remains to be clarified.

Item Type:Doctoral Thesis
ID Code:11083
Contributors:Glorioso, Nicola
Publisher:Universita' degli studi di Sassari
Uncontrolled Keywords:Essential hypertension, thiazides diutetics, genome-wide association study
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Cicli, scuole e corsi:Ciclo 27 > Scienze biomediche > Fisiopatologia medica
Deposited On:02 May 2016 17:39

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