Biography

Erika Salvi published latest article in Hypertension (Dallas, Tex. : 1979) entitled Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide. This article is available in PubMed with an unique identification number PMID: 27802415 and it is published in 2017. The coauthors of this article are Salvi, E; Wang, Z; Rizzi, F; Gong, Y; McDonough, CW; Padmanabhan, S; Hiltunen, TP; Lanzani, C; Zaninello, R; Chittani, M; Bailey, KR; Sarin, AP; Barcella, M; Melander, O; Chapman, AB; Manunta, P; Kontula, KK; Glorioso, N; Cusi, D; Dominiczak, AF; Johnson, JA; Barlassina, C; Boerwinkle, E; Cooper-DeHoff, RM; Turner, ST.


Research Interest

Veterinary Science


Latest Publication Details

Article Title: Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.

Co-Author(s): Salvi, E; Wang, Z; Rizzi, F; Gong, Y; McDonough, CW; Padmanabhan, S; Hiltunen, TP; Lanzani, C; Zaninello, R; Chittani, M; Bailey, KR; Sarin, AP; Barcella, M; Melander, O; Chapman, AB; Manunta, P; Kontula, KK; Glorioso, N; Cusi, D; Dominiczak, AF; Johnson, JA; Barlassina, C; Boerwinkle, E; Cooper-DeHoff, RM; Turner, ST

Affiliation(s): From the Department of Health Sciences, University of Milan, Italy (E.S., F.R., M.C., M.B., C.B.); Human Genetics and Institute of Molecular Medicine, University of Texas Health Science Center, Houston (Z.W., E.B.); Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy (Y.G., C.W.M., J.A.J., R.M.C.-D.) and Division of Cardiovascular Medicine, Department of Medicine (J.A.J., R.M.C.-D.), University of Florida, Gainesville; Institute of Cardiovascular and Medical Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, United Kingdom (S.P., A.F.D.); Department of Medicine, University of Helsinki and Helsinki University Hospital, Finland (T.P.H., K.K.K.); Nephrology and Dialysis and Hypertension Unit, San Raffaele Scientific Institute, Universit? Vita Salute San Raffaele, Milano, Italy (C.L., P.M.); Hypertension and Related Disease Centre, AOU-University of Sassari, Italy (R.Z., N.G.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension, Department of Internal Medicine (S.T.T.), Mayo Clinic, Rochester, Minnesota; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland (A.-P.S); Department of Clinical Sciences, Lund University, Malm?, Sweden (O.M.); Section of Nephrology, Department of Medicine, University of Chicago, Illinois (A.B.C.); Institute of Biomedical Technologies, National Research Centre of Italy, Segrate, Milan, Italy (D.C.); and Sanipedia srl, Bresso, Italy (D.C.). erika.salvi@unimi.it.

PMID 27802415, Year 2017

Abstract: This study aimed to identify novel loci influencing the antihypertensive response to hydrochlorothiazide monotherapy. A genome-wide meta-analysis of blood pressure (BP) response to hydrochlorothiazide was performed in 1739 white hypertensives from 6 clinical trials within the International Consortium for Antihypertensive Pharmacogenomics Studies, making it the largest study to date of its kind. No signals reached genome-wide significance (P<5?10-8), and the suggestive regions (P<10-5) were cross-validated in 2 black cohorts treated with hydrochlorothiazide. In addition, a gene-based analysis was performed on candidate genes with previous evidence of involvement in diuretic response, in BP regulation, or in hypertension susceptibility. Using the genome-wide meta-analysis approach, with validation in blacks, we identified 2 suggestive regulatory regions linked to gap junction protein ?1 gene (GJA1) and forkhead box A1 gene (FOXA1), relevant for cardiovascular and kidney function. With the gene-based approach, we identified hydroxy-delta-5-steroid dehydrogenase, 3 ?- and steroid ?-isomerase 1 gene (HSD3B1) as significantly associated with BP response (P<2.28?10-4). HSD3B1 encodes the 3?-hydroxysteroid dehydrogenase enzyme and plays a crucial role in the biosynthesis of aldosterone and endogenous ouabain. By amassing all of the available pharmacogenomic studies of BP response to hydrochlorothiazide, and using 2 different analytic approaches, we identified 3 novel loci influencing BP response to hydrochlorothiazide. The gene-based analysis, never before applied to pharmacogenomics of antihypertensive drugs to our knowledge, provided a powerful strategy to identify a locus of interest, which was not identified in the genome-wide meta-analysis because of high allelic heterogeneity. These data pave the way for future investigations on new pathways and drug targets to enhance the current understanding of personalized antihypertensive treatment.

Journal: Hypertension (Dallas, Tex. : 1979)

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