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.
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.
Authors: Hong Wei; Djahida Bedja; Norimichi Koitabashi; Dongmei Xing; Jasper Chen; Karen Fox-Talbot; Rosanne Rouf; Shaoping Chen; Charles Steenbergen; John W Harmon; Harry C Dietz; Kathleen L Gabrielson; David A Kass; Gregg L Semenza Journal: Proc Natl Acad Sci U S A Date: 2012-03-08 Impact factor: 11.205
Authors: Alexey Y Kolyada; Hocine Tighiouart; Mary C Perianayagam; Orfeas Liangos; Nicolaos E Madias; Bertrand L Jaber Journal: Kidney Int Date: 2009-03-11 Impact factor: 10.612
Authors: Monique Silter; Harald Kögler; Anke Zieseniss; Jörg Wilting; Katrin Schäfer; Karl Toischer; Adam G Rokita; Gerhard Breves; Lars S Maier; Dörthe M Katschinski Journal: Pflugers Arch Date: 2009-11-08 Impact factor: 3.657