Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans
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...
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| Format: | Online |
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Nature Publishing Group
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812324/ |
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pubmed-38123242014-03-20 Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans Del-Aguila, J L Beitelshees, A L Cooper-DeHoff, R M Chapman, A B Gums, J G Bailey, K Gong, Y Turner, S T Johnson, J A Boerwinkle, E Original Article 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 (r2=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. Nature Publishing Group 2014-02 2013-02-12 /pmc/articles/PMC3812324/ /pubmed/23400010 http://dx.doi.org/10.1038/tpj.2013.3 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Del-Aguila, J L Beitelshees, A L Cooper-DeHoff, R M Chapman, A B Gums, J G Bailey, K Gong, Y Turner, S T Johnson, J A Boerwinkle, E |
| spellingShingle |
Del-Aguila, J L Beitelshees, A L Cooper-DeHoff, R M Chapman, A B Gums, J G Bailey, K Gong, Y Turner, S T Johnson, J A Boerwinkle, E Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans |
| author_facet |
Del-Aguila, J L Beitelshees, A L Cooper-DeHoff, R M Chapman, A B Gums, J G Bailey, K Gong, Y Turner, S T Johnson, J A Boerwinkle, E |
| author_sort |
Del-Aguila, J L |
| title |
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans |
| title_short |
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans |
| title_full |
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans |
| title_fullStr |
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans |
| title_full_unstemmed |
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans |
| title_sort |
genome-wide association analyses suggest nell1 influences adverse metabolic response to hctz in african americans |
| description |
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 (r2=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. |
| publisher |
Nature Publishing Group |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812324/ |
| _version_ |
1612021693194174464 |