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1. TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives

Author

Chittani, Martina, primary, Zaninello, Roberta, additional, Lanzani, Chiara, additional, Frau, Francesca, additional, Ortu, Maria F., additional, Salvi, Erika, additional, Fresu, Giovanni, additional, Citterio, Lorena, additional, Braga, Daniele, additional, Piras, Daniela A., additional, Carpini, Simona Delli, additional, Velayutham, Dinesh, additional, Simonini, Marco, additional, Argiolas, Giuseppe, additional, Pozzoli, Simona, additional, Troffa, Chiara, additional, Glorioso, Valeria, additional, Kontula, Kimmo K., additional, Hiltunen, Timo P., additional, Donner, Kati M., additional, Turner, Stephen T., additional, Boerwinkle, Eric, additional, Chapman, Arlene B., additional, Padmanabhan, Sandosh, additional, Dominiczak, Anna F., additional, Melander, Olle, additional, Johnson, Julie A., additional, Cooper-Dehoff, Rhonda M., additional, Gong, Yan, additional, Rivera, Natalia V., additional, Condorelli, Gianluigi, additional, Trimarco, Bruno, additional, Manunta, Paolo, additional, Cusi, Daniele, additional, Glorioso, Nicola, additional, and Barlassina, Cristina, additional

Published
2015
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3. Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase

Author

Salvi, Erika, primary, Kutalik, Zoltán, additional, Glorioso, Nicola, additional, Benaglio, Paola, additional, Frau, Francesca, additional, Kuznetsova, Tatiana, additional, Arima, Hisatomi, additional, Hoggart, Clive, additional, Tichet, Jean, additional, Nikitin, Yury P., additional, Conti, Costanza, additional, Seidlerova, Jitka, additional, Tikhonoff, Valérie, additional, Stolarz-Skrzypek, Katarzyna, additional, Johnson, Toby, additional, Devos, Nabila, additional, Zagato, Laura, additional, Guarrera, Simonetta, additional, Zaninello, Roberta, additional, Calabria, Andrea, additional, Stancanelli, Benedetta, additional, Troffa, Chiara, additional, Thijs, Lutgarde, additional, Rizzi, Federica, additional, Simonova, Galina, additional, Lupoli, Sara, additional, Argiolas, Giuseppe, additional, Braga, Daniele, additional, D'Alessio, Maria C., additional, Ortu, Maria F., additional, Ricceri, Fulvio, additional, Mercurio, Maurizio, additional, Descombes, Patrick, additional, Marconi, Maurizio, additional, Chalmers, John, additional, Harrap, Stephen, additional, Filipovsky, Jan, additional, Bochud, Murielle, additional, Iacoviello, Licia, additional, Ellis, Justine, additional, Stanton, Alice V., additional, Laan, Maris, additional, Padmanabhan, Sandosh, additional, Dominiczak, Anna F., additional, Samani, Nilesh J., additional, Melander, Olle, additional, Jeunemaitre, Xavier, additional, Manunta, Paolo, additional, Shabo, Amnon, additional, Vineis, Paolo, additional, Cappuccio, Francesco P., additional, Caulfield, Mark J., additional, Matullo, Giuseppe, additional, Rivolta, Carlo, additional, Munroe, Patricia B., additional, Barlassina, Cristina, additional, Staessen, Jan A., additional, Beckmann, Jacques S., additional, and Cusi, Daniele, additional

Published
2012
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4. Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase

Author

Salvi, Erika, Kutalik, Zoltán, Glorioso, Nicola, Benaglio, Paola, Frau, Francesca, Kuznetsova, Tatiana, Arima, Hisatomi, Hoggart, Clive, Tichet, Jean, Nikitin, Yury P., Conti, Costanza, Seidlerova, Jitka, Tikhonoff, Valérie, Stolarz-Skrzypek, Katarzyna, Johnson, Toby, Devos, Nabila, Zagato, Laura, Guarrera, Simonetta, Zaninello, Roberta, Calabria, Andrea, Stancanelli, Benedetta, Troffa, Chiara, Thijs, Lutgarde, Rizzi, Federica, Simonova, Galina, Lupoli, Sara, Argiolas, Giuseppe, Braga, Daniele, D'Alessio, Maria C., Ortu, Maria F., Ricceri, Fulvio, Mercurio, Maurizio, Descombes, Patrick, Marconi, Maurizio, Chalmers, John, Harrap, Stephen, Filipovsky, Jan, Bochud, Murielle, Iacoviello, Licia, Ellis, Justine, Stanton, Alice V., Laan, Maris, Padmanabhan, Sandosh, Dominiczak, Anna F., Samani, Nilesh J., Melander, Olle, Jeunemaitre, Xavier, Manunta, Paolo, Shabo, Amnon, Vineis, Paolo, Cappuccio, Francesco P., Caulfield, Mark J., Matullo, Giuseppe, Rivolta, Carlo, Munroe, Patricia B., Barlassina, Cristina, Staessen, Jan A., Beckmann, Jacques S., and Cusi, Daniele

Subjects
3. Good health

5. Sex-Specific Effects of NLRP6/AVR and ADM Loci on Susceptibility to Essential Hypertension in a Sardinian Population.

Author

Glorioso, Nicola, Herrera, Victoria L., Didishvili, Tamara, Ortu, Maria F., Zaninello, Roberta, Fresu, Giovanni, Argiolas, Guiseppe, Troffa, Chiara, and Ruiz-Opazo, Nelson

Subjects
HYPERTENSION, DISEASE susceptibility, IMMUNE system, CORONARY disease, STROKE, ARRHYTHMIA
Abstract

Coronary artery disease, heart failure, fatal arrhythmias, stroke, and renal disease are the most common causes of mortality for humans, and essential hypertension remains a major risk factor. Elucidation of susceptibility loci for essential hypertension has been difficult because of its complex, multifactorial nature involving genetic, environmental, and sex- and age-dependent nature. We investigated whether the 11p15.5 region syntenic to rat chromosome 1 region containing multiple blood pressure quantitative trait loci (QTL) detected in Dahl rat intercrosses harbors polymorphisms that contribute to susceptibility/resistance to essential hypertension in a Sardinian population. Initial testing performed using microsatellite markers spanning 18 Mb of 11p15.5 detected a strong association between D11S1318 (at 2.1 Mb, P = 0.004) and D11S1346 (at 10.6 Mb, P = 0.00000004), suggesting that loci in close proximity to these markers may contribute to susceptibility in our Sardinian cohort. NLR family, pyrin domain containing 6/angiotensin-vasopressin receptor (NLRP6/AVR), and adrenomedullin (ADM) are in close proximity to D11S1318 and D11S1346, respectively; thus we tested single nucleotide polymorphisms (SNPs) within NLRP6/AVR and ADM for their association with hypertension in our Sardinian cohort. Upon sex stratification, we detected one NLRP6/AVR SNP associated with decreased susceptibility to hypertension in males (rs7948797G, P = 0.029; OR = 0.73 [0.57–0.94]). For ADM, sex-specific analysis showed a significant association between rs4444073C, with increased susceptibility to essential hypertension only in the male population (P = 0.006; OR = 1.44 [1.13–1.84]). Our results revealed an association between NLRP6/AVR and ADM loci with male essential hypertension, suggesting the existence of sex-specific NLRP6/AVR and ADM variants affecting male susceptibility to essential hypertension. [ABSTRACT FROM AUTHOR]

Published
2013
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6. TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives

Author

Simona Delli Carpini, Eric Boerwinkle, Erika Salvi, Gianluigi Condorelli, Marco Simonini, Lorena Citterio, Giovanni Fresu, Giuseppe Argiolas, Yan Gong, Sandosh Padmanabhan, Roberta Zaninello, Daniele Cusi, Anna F. Dominiczak, Daniela Antonella Piras, Maria Francesca Ortu, Dinesh Velayutham, Julie A. Johnson, Timo P. Hiltunen, Chiara Troffa, Rhonda M. Cooper-DeHoff, Chiara Lanzani, Bruno Trimarco, S. Pozzoli, Kati Donner, Daniele Braga, Nicola Glorioso, Martina Chittani, Kimmo Kontula, Cristina Barlassina, Arlene B. Chapman, Olle Melander, Francesca Frau, Paolo Manunta, Natalia V. Rivera, Valeria Glorioso, Stephen T. Turner, Chittani, Martina, Zaninello, Roberta, Lanzani, Chiara, Frau, Francesca, Ortu, Maria F, Salvi, Erika, Fresu, Giovanni, Citterio, Lorena, Braga, Daniele, Piras, Daniela A, Carpini, Simona Delli, Velayutham, Dinesh, Simonini, Marco, Argiolas, Giuseppe, Pozzoli, Simona, Troffa, Chiara, Glorioso, Valeria, Kontula, Kimmo K, Hiltunen, Timo P, Donner, Kati M, Turner, Stephen T, Boerwinkle, Eric, Chapman, Arlene B, Padmanabhan, Sandosh, Dominiczak, Anna F, Melander, Olle, Johnson, Julie A, Cooper Dehoff, Rhonda M, Gong, Yan, Rivera, Natalia V, Condorelli, Gianluigi, Trimarco, Bruno, Manunta, Paolo, Cusi, Daniele, Glorioso, Nicola, Barlassina, Cristina, Chittani, M, Zaninello, R, Lanzani, C, Frau, F, Ortu, Mf, Salvi, E, Fresu, G, Citterio, L, Braga, D, Piras, Da, Carpini, Sd, Velayutham, D, Simonini, M, Argiolas, G, Pozzoli, S, Troffa, C, Glorioso, V, Kontula, Kk, Hiltunen, Tp, Donner, Km, Turner, St, Boerwinkle, E, Chapman, Ab, Padmanabhan, S, Dominiczak, Af, Melander, O, Johnson, Ja, COOPER DEHOFF, Rm, Gong, Y, Rivera, Nv, Condorelli, G, Trimarco, B, Cusi, D, Glorioso, N, and Barlassina, C.

Subjects
Adult, Male, Physiology, medicine.drug_class, Systole, Sodium Chloride Symporter Inhibitors, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, Pharmacology, Essential hypertension, Article, Losartan, White People, Dioxygenases, 03 medical and health sciences, 0302 clinical medicine, Hydrochlorothiazide, Proto-Oncogene Proteins, Internal Medicine, Medicine, Humans, Antihypertensive drug, Aldosterone, Thiazide, Antihypertensive Agents, 030304 developmental biology, Aged, 0303 health sciences, business.industry, Tumor Suppressor Proteins, Membrane Proteins, Middle Aged, medicine.disease, 3. Good health, DNA-Binding Proteins, Italy, Pharmacogenetics, Pharmacogenomics, Case-Control Studies, Hypertension, Essential Hypertension, Cardiology and Cardiovascular Medicine, business, medicine.drug, Genome-Wide Association Study
Abstract

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.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.This exploratory study reports two plausible loci associated with SBP response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of αENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case-control study.

Published
2015

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