Level A· Stronger Clinical EvidenceMeta-analysisEurope PMCOpen access

Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans

Del-Aguila JL., Beitelshees AL., Cooper-Dehoff RM., Chapman AB., Gums JG., Bailey K.

Meta-analysis, published in Pharmacogenomics J (2014) — summary generated from the PubMed abstract.

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Level A· Stronger Clinical EvidenceEvidence level of this study

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

  • Level A · Stronger Clinical Evidence
  • Level B · Emerging clinical evidence with positive signals
  • Level C · Early human research exploring benefits
  • Level D · Scientific groundwork from lab and animal studies
  • Emerging · Emerging topic under active research
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This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.

Study type
Meta-analysis
Journal
Pharmacogenomics J (2014)
Reported sample size
—
Source database
Europe PMC
PMID
23400010
PMCID
PMC3812324
DOI
10.1038/tpj.2013.3
Citations
36

Abstract (original English)

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.

What this study does not prove

  • • This study does not prove SVF is an approved treatment or a replacement for standard care.

Evidence level

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

How we grade evidence
HumansHypertensionHydrochlorothiazideBlood GlucoseTriglyceridesCalcium-Binding ProteinsNerve Tissue ProteinsAntihypertensive AgentsAdipogenesisLipid Metabolism

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