Trial reportJournal of translational medicine2012
Effects of genetic variation in H3K79 methylation regulatory genes on clinical blood pressure and blood pressure response to hydrochlorothiazide.
Trial report in Journal of translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 19 papers.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetic Epidemiology of Responses to Antihypertensives
Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR)
Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.Journal of hypertension · 2015Trial
- Article
- Roles and mechanisms of histone methylation in vascular aging and related diseases.Clinical epigenetics · 2025Review
- Summary of Known Genetic and Epigenetic Modification Contributed to Hypertension.International journal of hypertension · 2023Review
- Clinical epigenomics for cardiovascular disease: Diagnostics and therapies.Journal of molecular and cellular cardiology · 2021Review
- Epigenetic modification: a regulatory mechanism in essential hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Review
- ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.Journal of the American Heart Association · 2019Article
- Pharmacogenomics of amlodipine and hydrochlorothiazide therapy and the quest for improved control of hypertension: a mini review.Heart failure reviews · 2019Review
- Epigenetic Biomarkers in Cardiovascular Diseases.Frontiers in genetics · 2019Review
- Epigenetics and precision medicine in cardiovascular patients: from basic concepts to the clinical arena.European heart journal · 2018Review
- Protein kinase Cα deletion causes hypotension and decreased vascular contractility.Journal of hypertension · 2018Article
- TALEN-Mediated FLAG-Tagging of Endogenous Histone Methyltransferase DOT1L.Advances in bioscience and biotechnology (Print) · 2017Article
- Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis.International journal of molecular sciences · 2016Review
- Epigenetic Modifications in Essential Hypertension.International journal of molecular sciences · 2016Review
- Regulation of αENaC transcription.Vitamins and hormones · 2015Review
- Mineralocorticoid receptor antagonizes Dot1a-Af9 complex to increase αENaC transcription.American journal of physiology. Renal physiology · 2013Article
- Physical and functional interaction of Rnf2 with Af9 regulates basal and aldosterone-stimulated transcription of the α-ENaC gene in a renal collecting duct cell line.Bioscience reports · 2013Article
- Epigenetics and the control of the collecting duct epithelial sodium channel.Seminars in nephrology · 2013Review
- An Af9 cis-element directly targets Dot1a to mediate transcriptional repression of the αENaC gene.American journal of physiology. Renal physiology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundNearly one-third of the United States adult population suffers from hypertension. Hydrochlorothiazide (HCTZ), one of the most commonly used medications to treat hypertension, has variable efficacy. The renal epithelial sodium channel (ENaC) provides a mechanism for fine-tuning sodium excretion, and is a major regulator of blood pressure homeostasis. DOT1L, MLLT3, SIRT1, and SGK1 encode genes in a pathway that controls methylation of the histone H3 globular domain at lysine 79 (H3K79), thereby modulating expression of the ENaCα subunit. This study aimed to determine the role of variation in these regulatory genes on blood pressure response to HCTZ, and secondarily, untreated blood pressure.
methodsWe investigated associations between genetic variations in this candidate pathway and HCTZ blood pressure response in two separate hypertensive cohorts (clinicaltrials.gov NCT00246519 and NCT00005520). In a secondary, exploratory analysis, we measured associations between these same genetic variations and untreated blood pressure. Associations were measured by linear regression, with only associations with P ≤ 0.01 in one cohort and replication by P ≤ 0.05 in the other cohort considered significant.
resultsIn one cohort, a polymorphism in DOT1L (rs2269879) was strongly associated with greater systolic (P = 0.0002) and diastolic (P = 0.0016) blood pressure response to hydrochlorothiazide in Caucasians. However, this association was not replicated in the other cohort. When untreated blood pressure levels were analyzed, we found directionally similar associations between a polymorphism in MLLT3 (rs12350051) and greater untreated systolic (P < 0.01 in both cohorts) and diastolic (P < 0.05 in both cohorts) blood pressure levels in both cohorts. However, when further replication was attempted in a third hypertensive cohort and in smaller, normotensive samples, significant associations were not observed.
conclusionsOur data suggest polymorphisms in DOT1L, MLLT3, SIRT1, and SGK1 are not likely associated with blood pressure response to HCTZ. However, a possibility exists that rs2269879 in DOT1L could be associated with HCTZ response in Caucasians. Additionally, exploratory analyses suggest rs12350051 in MLLT3 may be associated with untreated blood pressure in African-Americans. Replication efforts are needed to verify roles for these polymorphisms in human blood pressure regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.