title: A functionally significant polymorphism in ID3 is associated with human coronary pathology.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America; Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Heather
authors.initials: H
authors.lastname: Perry
authors.affiliation: Department of Internal Medicine/Cardiology, Wake Forest University Health Sciences, Winston Salem, North Carolina, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Yeboah
authors.affiliation: Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America; Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Law
authors.affiliation: Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Molly
authors.initials: M
authors.lastname: Davis
authors.affiliation: Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Parker
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Ragosta
authors.affiliation: Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America; Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Connelly
authors.affiliation: Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America; Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Coleen A
authors.initials: CA
authors.lastname: McNamara
authors.affiliation: Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America; Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Taylor
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C075640:ID3 protein, human