title: Hypoxia-inducible factor 1alpha polymorphism and coronary collaterals in patients with ischemic heart disease.
abstract: OBJECTIVE
  Marked variability exists in coronary artery collaterals in patients with ischemic heart disease. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors is largely unknown. Hypoxia inducible factor 1 (HIF-1), a transcriptional activator that functions as a master regulator of oxygen homeostasis, is one possible genetic factor that could play an important role in modulating collateral development.
  
  
  METHODS
  Collateral vessels were determined in 100 patients with > or = 70% narrowing of at least one coronary artery without acute myocardial infarction or prior revascularization. DNA was genotyped for the presence of a single nucleotide (C to T) polymorphism that changes residue 582 of HIF-1alpha from proline to serine.
  
  
  RESULTS
  The frequency of the T allele was significantly higher among patients without collaterals compared to patients with collaterals (0.188 vs 0.037, p < 0.001). In multivariate analyses, two variables affecting collateral formation were detected: two- or three-vessel coronary artery disease was a significant positive predictor (odds ratio [OR], 4.17; 95% confidence interval [CI], 1.61 to 10.8; p = 0.001), whereas the presence of HIF-1alpha genotype CT or TT was a negative predictor (OR, 0.19; 95% CI, 0.04 to 0.84; p = 0.03).
  
  
  CONCLUSIONS
  These data suggest that variations in HIF-1alpha genotype may influence development of coronary artery collaterals in patients with significant coronary artery disease.
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Blalock 524, 600 North Wolfe St, Baltimore, MD 21287, USA. jresar@jhmi.edu
authors.forename: Jon R
authors.initials: JR
authors.lastname: Resar
authors.forename: Ariel
authors.initials: A
authors.lastname: Roguin
authors.forename: Jeffery
authors.initials: J
authors.lastname: Voner
authors.forename: Khurram
authors.initials: K
authors.lastname: Nasir
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hennebry
authors.forename: Julie M
authors.initials: JM
authors.lastname: Miller
authors.forename: Roxann
authors.initials: R
authors.lastname: Ingersoll
authors.forename: Laura M
authors.initials: LM
authors.lastname: Kasch
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003097:Collateral Circulation / Q000235:genetics*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics*; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors