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

Keywords

  • Collaterals
  • Genetics
  • Genotype
  • Ischemia

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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