Hypoxia-inducible factor 1α polymorphism and coronary collaterals in patients with ischemic heart disease

Jon R Resar, Ariel Roguin, Jeffery Voner, Khurram Nasir, Thomas A. Hennebry, Julie M Miller, Roxann Ingersoll, Laura M. Kasch, Gregg L Semenza

Research output: Contribution to journalArticle

Abstract

Study objectives: 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. Design, setting, and participants: Collateral vessels were determined in 100 patients with ≥ 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-1α from proline to serine. Measurements and 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-1α 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-1α genotype may influence development of coronary artery collaterals in patients with significant coronary artery disease.

Original languageEnglish (US)
Pages (from-to)787-791
Number of pages5
JournalChest
Volume128
Issue number2
DOIs
StatePublished - Aug 2005

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Hypoxia-Inducible Factor 1
Myocardial Ischemia
Coronary Vessels
Coronary Artery Disease
Odds Ratio
Genotype
Activator Appliances
Confidence Intervals
Proline
Gene Frequency
Serine
Homeostasis
Multivariate Analysis
Nucleotides
Myocardial Infarction
Oxygen
DNA

Keywords

  • Collaterals
  • Genetics
  • Genotype
  • Ischemia

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Hypoxia-inducible factor 1α polymorphism and coronary collaterals in patients with ischemic heart disease. / Resar, Jon R; Roguin, Ariel; Voner, Jeffery; Nasir, Khurram; Hennebry, Thomas A.; Miller, Julie M; Ingersoll, Roxann; Kasch, Laura M.; Semenza, Gregg L.

In: Chest, Vol. 128, No. 2, 08.2005, p. 787-791.

Research output: Contribution to journalArticle

Resar, Jon R ; Roguin, Ariel ; Voner, Jeffery ; Nasir, Khurram ; Hennebry, Thomas A. ; Miller, Julie M ; Ingersoll, Roxann ; Kasch, Laura M. ; Semenza, Gregg L. / Hypoxia-inducible factor 1α polymorphism and coronary collaterals in patients with ischemic heart disease. In: Chest. 2005 ; Vol. 128, No. 2. pp. 787-791.
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