TY - JOUR
T1 - TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives
AU - Chittani, Martina
AU - Zaninello, Roberta
AU - Lanzani, Chiara
AU - Frau, Francesca
AU - Ortu, Maria F.
AU - Salvi, Erika
AU - Fresu, Giovanni
AU - Citterio, Lorena
AU - Braga, Daniele
AU - Piras, Daniela A.
AU - Delli Carpini, Simona
AU - Velayutham, Dinesh
AU - Simonini, Marco
AU - Argiolas, Giuseppe
AU - Pozzoli, Simona
AU - Troffa, Chiara
AU - Glorioso, Valeria
AU - Kontula, Kimmo K.
AU - Hiltunen, Timo P.
AU - Donner, Kati M.
AU - Turner, Stephen T.
AU - Boerwinkle, Eric
AU - Chapman, Arlene B.
AU - Padmanabhan, Sandosh
AU - Dominiczak, Anna F.
AU - Melander, Olle
AU - Johnson, Julie A.
AU - Cooper-Dehoff, Rhonda M.
AU - Gong, Yan
AU - Rivera, Natalia V.
AU - Condorelli, Gianluigi
AU - Trimarco, Bruno
AU - Manunta, Paolo
AU - Cusi, Daniele
AU - Glorioso, Nicola
AU - Barlassina, Cristina
N1 - Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015/6/6
Y1 - 2015/6/6
N2 - Background: Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects. Methods and results: We looked for variants associated with blood pressure response to hydrochlorothiazide over an 8-week follow-up by means of a genome-wide association analysis in two Italian cohorts of never-treated essential hypertensive patients: 343 samples from Sardinia and 142 from Milan. TET2 and CSMD1 as plausible candidate genes to affect SBP response to hydrochlorothiazide were identified. The specificity of our findings for hydrochlorothiazide was confirmed in an independent cohort of essential hypertensive patients treated with losartan. Our best findings were also tested for replication in four independent hypertensive samples of European Ancestry, such as GENetics of drug RESponsiveness in essential hypertension, Genetic Epidemiology of Responses to Antihypertensives, NORdic DILtiazem intervention, Pharmacogenomics Evaluation of Antihypertensive Responses, and Campania Salute Network-StayOnDiur. We validated a polymorphism in CSMD1 and UGGT2. Conclusion: This exploratory study reports two plausible loci associated with SBP response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of ENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case-control study.
AB - Background: Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects. Methods and results: We looked for variants associated with blood pressure response to hydrochlorothiazide over an 8-week follow-up by means of a genome-wide association analysis in two Italian cohorts of never-treated essential hypertensive patients: 343 samples from Sardinia and 142 from Milan. TET2 and CSMD1 as plausible candidate genes to affect SBP response to hydrochlorothiazide were identified. The specificity of our findings for hydrochlorothiazide was confirmed in an independent cohort of essential hypertensive patients treated with losartan. Our best findings were also tested for replication in four independent hypertensive samples of European Ancestry, such as GENetics of drug RESponsiveness in essential hypertension, Genetic Epidemiology of Responses to Antihypertensives, NORdic DILtiazem intervention, Pharmacogenomics Evaluation of Antihypertensive Responses, and Campania Salute Network-StayOnDiur. We validated a polymorphism in CSMD1 and UGGT2. Conclusion: This exploratory study reports two plausible loci associated with SBP response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of ENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case-control study.
KW - essential hypertension
KW - genome-wide association study
KW - genomics
KW - pharmacogenomics
KW - thiazides diuretics
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U2 - 10.1097/HJH.0000000000000541
DO - 10.1097/HJH.0000000000000541
M3 - Article
C2 - 25695618
AN - SCOPUS:84929458153
SN - 0263-6352
VL - 33
SP - 1301
EP - 1309
JO - Journal of hypertension
JF - Journal of hypertension
IS - 6
ER -