Hypoxia-inducible Factor 1alpha Polymorphism and Coronary Collaterals in Patients with Ischemic Heart Disease

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 > 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.

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-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.