A functionally significant polymorphism in ID3 is associated with human coronary pathology.
<h4>Aims</h4>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, at...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090222&type=printable |
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| author | Ani Manichaikul Stephen S Rich Heather Perry Joseph Yeboah Michelle Law Molly Davis Matthew Parker Michael Ragosta Jessica J Connelly Coleen A McNamara Angela M Taylor |
| author_facet | Ani Manichaikul Stephen S Rich Heather Perry Joseph Yeboah Michelle Law Molly Davis Matthew Parker Michael Ragosta Jessica J Connelly Coleen A McNamara Angela M Taylor |
| author_sort | Ani Manichaikul |
| collection | DOAJ |
| description | <h4>Aims</h4>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.<h4>Methods and results</h4>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).<h4>Conclusions</h4>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 | Article |
| id | doaj-art-3bae6df22156477eb4d7bf8f07e8f80b |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-3bae6df22156477eb4d7bf8f07e8f80b2025-08-20T03:46:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9022210.1371/journal.pone.0090222A functionally significant polymorphism in ID3 is associated with human coronary pathology.Ani ManichaikulStephen S RichHeather PerryJoseph YeboahMichelle LawMolly DavisMatthew ParkerMichael RagostaJessica J ConnellyColeen A McNamaraAngela M Taylor<h4>Aims</h4>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.<h4>Methods and results</h4>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).<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090222&type=printable |
| spellingShingle | Ani Manichaikul Stephen S Rich Heather Perry Joseph Yeboah Michelle Law Molly Davis Matthew Parker Michael Ragosta Jessica J Connelly Coleen A McNamara Angela M Taylor A functionally significant polymorphism in ID3 is associated with human coronary pathology. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090222&type=printable |
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