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A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology
AIMS: We previously identified association between the ID3 SNP rs11574 and carotid intima-media thickness in the Diabetes Heart Study, a predominantly White diabetic population. The nonsynonymous SNP rs11574 results in an amino acid substitution in the C-terminal region of ID3, attenuating the domin...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946163/ https://www.ncbi.nlm.nih.gov/pubmed/24603695 http://dx.doi.org/10.1371/journal.pone.0090222 |
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author | Manichaikul, Ani Rich, Stephen S. Perry, Heather Yeboah, Joseph Law, Michelle Davis, Molly Parker, Matthew Ragosta, Michael Connelly, Jessica J. McNamara, Coleen A. Taylor, Angela M. |
author_facet | Manichaikul, Ani Rich, Stephen S. Perry, Heather Yeboah, Joseph Law, Michelle Davis, Molly Parker, Matthew Ragosta, Michael Connelly, Jessica J. McNamara, Coleen A. Taylor, Angela M. |
author_sort | Manichaikul, Ani |
collection | PubMed |
description | AIMS: We previously identified association between the ID3 SNP rs11574 and carotid intima-media thickness in the Diabetes Heart Study, a predominantly White diabetic population. The nonsynonymous SNP rs11574 results in an amino acid substitution in the C-terminal region of ID3, attenuating the dominant negative function of ID3 as an inhibitor of basic HLH factor E12-mediated transcription. In the current investigation, we characterize the association between the functionally significant polymorphism in ID3, rs11574, with human coronary pathology. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal study of subclinical cardiovascular disease, including non-Hispanic White (n = 2,588), African American (n = 2,560) and Hispanic (n = 2,130) participants with data on coronary artery calcium (CAC). The Coronary Assessment in Virginia cohort (CAVA) included 71 patients aged 30–80 years, undergoing a medically necessary cardiac catheterization and intravascular ultrasound (IVUS) at the University of Virginia. ID3 SNP rs11574 risk allele was associated with the presence of CAC in MESA Whites (P = 0.017). In addition, the risk allele was associated with greater atheroma burden and stenosis in the CAVA cohort (P = 0.003, P = 0.04 respectively). The risk allele remained predictive of atheroma burden in multivariate analysis (Model 1: covariates age, gender, and LDL, regression coefficient = 9.578, SE = 3.657, p = 0.0110; Model 2: covariates Model 1, presence of hypertension, presence of diabetes, regression coefficient = 8.389, SE = 4.788, p = 0.0163). CONCLUSIONS: We present additional cohorts that demonstrate association of ID3 SNP rs11574 directly with human coronary artery pathology as measured by CAC and IVUS: one a multiethnic, relatively healthy population with low levels of diabetes and the second a predominantly White population with a higher incidence of T2DM referred for cardiac catheterization. |
format | Online Article Text |
id | pubmed-3946163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39461632014-03-12 A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology Manichaikul, Ani Rich, Stephen S. Perry, Heather Yeboah, Joseph Law, Michelle Davis, Molly Parker, Matthew Ragosta, Michael Connelly, Jessica J. McNamara, Coleen A. Taylor, Angela M. PLoS One Research Article AIMS: We previously identified association between the ID3 SNP rs11574 and carotid intima-media thickness in the Diabetes Heart Study, a predominantly White diabetic population. The nonsynonymous SNP rs11574 results in an amino acid substitution in the C-terminal region of ID3, attenuating the dominant negative function of ID3 as an inhibitor of basic HLH factor E12-mediated transcription. In the current investigation, we characterize the association between the functionally significant polymorphism in ID3, rs11574, with human coronary pathology. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal study of subclinical cardiovascular disease, including non-Hispanic White (n = 2,588), African American (n = 2,560) and Hispanic (n = 2,130) participants with data on coronary artery calcium (CAC). The Coronary Assessment in Virginia cohort (CAVA) included 71 patients aged 30–80 years, undergoing a medically necessary cardiac catheterization and intravascular ultrasound (IVUS) at the University of Virginia. ID3 SNP rs11574 risk allele was associated with the presence of CAC in MESA Whites (P = 0.017). In addition, the risk allele was associated with greater atheroma burden and stenosis in the CAVA cohort (P = 0.003, P = 0.04 respectively). The risk allele remained predictive of atheroma burden in multivariate analysis (Model 1: covariates age, gender, and LDL, regression coefficient = 9.578, SE = 3.657, p = 0.0110; Model 2: covariates Model 1, presence of hypertension, presence of diabetes, regression coefficient = 8.389, SE = 4.788, p = 0.0163). CONCLUSIONS: We present additional cohorts that demonstrate association of ID3 SNP rs11574 directly with human coronary artery pathology as measured by CAC and IVUS: one a multiethnic, relatively healthy population with low levels of diabetes and the second a predominantly White population with a higher incidence of T2DM referred for cardiac catheterization. Public Library of Science 2014-03-06 /pmc/articles/PMC3946163/ /pubmed/24603695 http://dx.doi.org/10.1371/journal.pone.0090222 Text en © 2014 Manichaikul et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Manichaikul, Ani Rich, Stephen S. Perry, Heather Yeboah, Joseph Law, Michelle Davis, Molly Parker, Matthew Ragosta, Michael Connelly, Jessica J. McNamara, Coleen A. Taylor, Angela M. A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology |
title | A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology |
title_full | A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology |
title_fullStr | A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology |
title_full_unstemmed | A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology |
title_short | A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology |
title_sort | functionally significant polymorphism in id3 is associated with human coronary pathology |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946163/ https://www.ncbi.nlm.nih.gov/pubmed/24603695 http://dx.doi.org/10.1371/journal.pone.0090222 |
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