Evidence map›Paper›PMID 40681478›Full record

ArticleClinical and translational science2025

Genetic Variation in Hydrochlorothiazide Response-Related Genes Among Hypertensive Individuals in Soweto, South Africa.

Kudakwashe Nyamupangedengu, David Twesigomwe, Andrew May, Collen Masimirembwa, Neil Martinson, Ziyaad Waja, Matebogo Letutu, Michèle Ramsay

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Article in Clinical and translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Kudakwashe NyamupangedenguSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0002-3877-2132
David TwesigomweSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0002-5421-5512
Andrew MaySydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0002-7045-1566
Collen MasimirembwaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0002-4053-212X
Neil MartinsonPerinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa.
Ziyaad WajaPerinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0001-8717-9039
Matebogo LetutuPerinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa.
Michèle RamsaySydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0002-4156-4801

Funding

South African Medical Research Council
6 · The paper itself

Abstract

Africa bears the largest burden of morbidity and mortality from hypertension (HT) and related cardiovascular diseases. Thiazide diuretics, including hydrochlorothiazide (HCTZ), are the most prescribed hypertension medicines globally due to their cost effectiveness and minimal side effects. However, studies investigating the genetic variation in HCTZ-related genes and their effect on drug response have been mainly conducted in European, American, and Asian populations. This study aimed to examine genetic variation in HCTZ response-related genes among newly diagnosed hypertensives from Soweto, South Africa, irrespective of the treatment approach, and to assess its potential impact on medication response. Using targeted NGS on 364 newly diagnosed hypertensives with at least one follow-up visit, we identified 1258 unique variants in 16 key HCTZ response genes. Among these, 89 were novel variants, of which 12 were protein-altering, including 8 predicted to be deleterious. Association analyses with 882 independent variants revealed that carriers of the intronic variant rs1025450259 in GNB3 had significantly greater reduction in BP compared to other patients on heterogeneous treatment strategies, but no significant associations were detected in the subset of individuals treated with HCTZ monotherapy only (n = 103). For variants previously associated with HCTZ response, we did not replicate prior associations (e.g., rs2611316 in ALDH1A2) but highlight important allele frequency differences across global populations. Despite the limitations, the study outcomes support the need for larger, controlled trials to assess genetic influences on HT treatment outcomes, advancing personalized medicine for African populations. This research further underscores the importance of pharmacogenetic studies in continental African populations.

Indexed as

Antihypertensive AgentsHydrochlorothiazideHypertensionPharmacogenomic VariantsAdultAgedBlood PressureFemaleHumansMaleMiddle AgedPolymorphism, Single NucleotideSouth AfricaTreatment OutcomeAntihypertensive AgentsHydrochlorothiazide

Identifiers

PMID40681478
PMCPMC12274112

What Socratic holds

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