SynthesisThe pharmacogenomics journal2014
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans.
Synthesis in The pharmacogenomics journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00246519 (Pharmacogenomic Evaluation of Antihypertensive Responses), which is not on this map. Cited by 26 papers, 2 of them syntheses that pooled 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.
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.
Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR)
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry.The pharmacogenomics journal · 2019Pooled it
- Pooled it
- Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation.Journal of lipid research · 2014Trial
- PROX1 gene variant is associated with fasting glucose change after antihypertensive treatment.Pharmacotherapy · 2014Trial
- Management of dyslipidaemia in patients with comorbidities-facing the challenge: heart failure.European heart journal. Cardiovascular pharmacotherapy · 2026Review
- NELL-1: role and mechanisms in disease pathogenesis and development.Frontiers in cell and developmental biology · 2026Review
- Sex-Biased Admixture Followed by Isolation and Adaptive Evolution Shaped the Genomic and Blood Pressure Diversity of the LopNur People.Molecular biology and evolution · 2025Article
- Antihypertensives associated adverse events: a review of mechanisms and pharmacogenomic biomarkers available evidence in multi-ethnic populations.Frontiers in pharmacology · 2023Review
- Semantic and Population Analysis of the Genetic Targets Related to COVID-19 and Its Association with Genes and Diseases.Advances in experimental medicine and biology · 2023Article
- Genetic Variants Associated with Adverse Events after Angiotensin-Converting Enzyme Inhibitor Use: Replication after GWAS-Based Discovery.Yonsei medical journal · 2022Article
- NELL-1 in Genome-Wide Association Studies across Human Diseases.The American journal of pathology · 2022Review
- Genome-wide association studies in Samoans give insight into the genetic architecture of fasting serum lipid levels.Journal of human genetics · 2021Article
- The Advantages and Challenges of Diversity in Pharmacogenomics: Can Minority Populations Bring Us Closer to Implementation?Clinical pharmacology and therapeutics · 2019Review
- Candidate Regulators of Dyslipidemia in Chromosome 1 Substitution Lines Using Liver Co-Expression Profiling Analysis.Frontiers in genetics · 2019Article
- Leaving some behind: the growing gap in precision medicine for minority populations.Expert review of precision medicine and drug development · 2019Article
- Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK activation and obesity-associated pathophysiology.Nature communications · 2018Article
- Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.The pharmacogenomics journal · 2018Article
- Pharmacogenomic studies of hypertension: paving the way for personalized antihypertensive treatment.Expert review of precision medicine and drug development · 2018Article
- Article
- Research Needs to Improve Hypertension Treatment and Control in African Americans.Hypertension (Dallas, Tex. : 1979) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 1 country.
Funding
Abstract
Hydrochlorothiazide (HCTZ) is one of the most widely prescribed antihypertensive medications. Although it is well known that HCTZ is associated with hyperglycemia and hypertriglyceridemia, the mechanisms underlying these adverse effects are not well understood. We performed a genome-wide association study and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses and the Genetic Epidemiology of Responses to Antihypertensive studies. Two single-nucleotide polymorphisms (rs12279250 and rs4319515 (r(2)=0.73)), located at 11p15.1 in the NELL1 gene, achieved genome-wide significance for association with change in fasting plasma triglycerides in African Americans, whereby each variant allele was associated with a 28 mg dl(-1) increase in the change in triglycerides. NELL1 encodes a cytoplasmic protein that contains epidermal growth factor-like repeats and has been shown to represses adipogenic differentiation. These findings may represent a novel mechanism underlying HCTZ-induced adverse metabolic effects.
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What OpenQuestion holds
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.