Hypoxia-inducible factor 1alpha polymorphism and coronary collaterals in patients with ischemic heart disease.
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.
Resar
Jon R
JR
Division of Cardiology, The Johns Hopkins University School of Medicine, Blalock 524, 600 North Wolfe St, Baltimore, MD 21287, USA. jresar@jhmi.edu
Roguin
Ariel
A
Voner
Jeffery
J
Nasir
Khurram
K
Hennebry
Thomas A
TA
Miller
Julie M
JM
Ingersoll
Roxann
R
Kasch
Laura M
LM
Semenza
Gregg L
GL
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*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors