{"id":"19ab7a4e2c0b","type":"article","url":"https://hartvaat.nl/2017/01/01/genoomwijde-meta-analyse-van-bloeddrukrespons-op-hydrochloorthiazide/","title":"Genoomwijde meta-analyse van bloeddrukrespons op hydrochloorthiazide","title_en":"Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.","category":"hypertensie","category_label":"Hypertensie","professions":["cardioloog","internist"],"tags":["bloeddrukbehandeling","vrouwen"],"journal":"Hypertension (Dallas, Tex. : 1979)","doi":"10.1161/HYPERTENSIONAHA.116.08267","source_url":"https://doi.org/10.1161/HYPERTENSIONAHA.116.08267","authors":["Erika Salvi","Zhiying Wang","Federica Rizzi","Yan Gong","Caitrin W McDonough","Sandosh Padmanabhan","Timo P Hiltunen","Chiara Lanzani","Roberta Zaninello","Martina Chittani","Kent R Bailey","Antti-Pekka Sarin","Matteo Barcella","Olle Melander","Arlene B Chapman","Paolo Manunta","Kimmo K Kontula","Nicola Glorioso","Daniele Cusi","Anna F Dominiczak","Julie A Johnson","Cristina Barlassina","Eric Boerwinkle","Rhonda M Cooper-DeHoff","Stephen T Turner"],"significance":5,"published":"2017-01-01","source_date":"2017-01-01","image":"","kennis":["https://hartvaat.nl/kennis/hypertensie/classificatie-bloeddruk-esc-2024/","https://hartvaat.nl/kennis/hypertensie/resistente-hypertensie/"],"congress":"","summary_en":"This genome-wide meta-analysis identified novel genetic loci influencing the antihypertensive response to hydrochlorothiazide, advancing pharmacogenomic approaches to personalized diuretic therapy selection.","created":"2026-07-03T10:26:29Z","updated":"2026-07-03T18:38:29Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Genoomwijde en gen-gebaseerde meta-analyse die nieuwe loci identificeerde die de bloeddrukrespons op hydrochloorthiazide beïnvloeden. Farmacogenomisch onderzoek naar gepersonaliseerde hypertensiebehandeling.","abstract_original":"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 α1 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 β- and steroid δ-isomerase 1 gene (HSD3B1) as significantly associated with BP response (P<2.28×10-4 ). HSD3B1 encodes the 3β-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."}