C677T polymorphism of the methylenetetrahydrofolate reductase gene is a risk factor of adverse events after coronary revascularization.
BACKGROUND
A common point mutation (C677T) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with hyperhomocysteinemia, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD). The aim of this study was to investigate whether C677T polymorphism can be a predictor of major adverse cardiac events after myocardial revascularization.


METHODS
We determined MTHFR genotype in 159 patients with CAD undergoing myocardial revascularization [72 percutaneous transluminal coronary angioplasty (PTCA) and 87 coronary artery bypass graft (CABG)]. Recurrent angina, nonfatal myocardial infarction (MI), target vessel revascularization, heart failure and cardiac death were considered major adverse cardiac events that occurred after discharge from index hospitalization.


RESULTS
During the follow-up (6.9+/-0.3 months, mean+/-S.E.M.), the composite endpoint accounted for 25.9%, 11.4% and 4.3% for TT, CT and CC genotype (log-rank statistic 5.2, p=0.02), respectively. Subjects with mutant TT genotype had a threefold increase of any cardiac event (hazard ratio [HR]=3.0; 95% [CI], 1.1-8.1). In multiple-variable regression Cox, predictors of events were TT genotype (HR=2.8; 95% CI, 1.01-7.62, p=0.047), low-ejection fraction<40% (HR=4.5; 95% CI, 1.62-12.6, p=0.004) and revascularization procedure (HR=6.1; 95% CI, 1.86-20.34, p=0.003).


CONCLUSIONS
These data indicate that the TT genotype seems to be significantly associated with major adverse cardiac events after myocardial revascularization in CAD patients, suggesting a potential pathological influence of homocysteine in the clinical outcome.
Botto
Nicoletta
N
CNR, Institute of Clinical Physiology, G. Pasquinucci Hospital, via Aurelia Sud-Montepepe 54100, Massa, Italy.
Andreassi
Maria Grazia
MG
Rizza
Antonio
A
Berti
Sergio
S
Bevilacqua
Stefano
S
Federici
Chiara
C
Palmieri
Cataldo
C
Glauber
Mattia
M
Biagini
Andrea
A
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000235:genetics* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012008:Recurrence; D012307:Risk Factors; D017211:Treatment Failure
D042965:Methylenetetrahydrofolate Reductase (NADPH2)