Haem oxygenase-1 genotype and cardiovascular adverse events in patients with peripheral artery disease.
BACKGROUND
A functional GT dinucleotide length polymorphism in the haem oxygenase-1 (HO-1) gene promoter is thought to be involved in the pathogenesis of cardiovascular disease. Short (< 25) (GT)n repeats are suggested to facilitate enhanced HO-1 up-regulation in response to injury and confer potent anti-inflammatory and antioxidative effects.


METHODS
We investigated the association between the HO-1 GT-polymorphism and cardiovascular outcome in 472 patients with advanced peripheral artery disease. Cardiovascular risk profile and DNA samples for determination of the HO-1 genotype (carrier vs. noncarrier of a short (GT)n repeat allele) were obtained at baseline, and patients were followed for median 21 months for the occurrence of coronary events (myocardial infarction, percutaneous coronary interventions and coronary artery bypass graft), cerebrovascular events (stroke or carotid revascularization) and all-cause mortality.


RESULTS
Coronary events occurred in 48 patients (9%), cerebrovascular events in 40 patients (9%) and 59 patients (13%) died. In total, 173 major adverse cardiovascular events (MACE) occurred in 133 patients (28%). Carriers of the short (GT)n repeat allele had a 0.46-fold reduced adjusted hazard ratio for coronary events (P = 0.016) as compared to noncarriers. No significant difference was found for cerebrovascular events, mortality and overall MACE.


CONCLUSIONS
Apparently, the HO-1 genotype exerts potentially protective effects against coronary adverse events in patients with peripheral artery disease. Homozygous and heterozygous carriers of < 25 (GT)n repeats had lower rates of myocardial infarction, percutaneous coronary interventions and coronary bypass operations compared to patients with longer (GT)n repeats.
Dick
P
P
Department of Angiology, Vienna General Hospital, Medical University Vienna, Austria, Europe.
Schillinger
M
M
Minar
E
E
Mlekusch
W
W
Amighi
J
J
Sabeti
S
S
Schlager
O
O
Raith
M
M
Endler
G
G
Mannhalter
C
C
Wagner
O
O
Exner
M
M
D000368:Aged; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000235:genetics* / Q000401:mortality; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D020521:Stroke / Q000235:genetics; D015996:Survival Rate
D051547:Heme Oxygenase-1