Role of methylenetetrahydrofolate reductase 677C->T polymorphism in the development of premature myocardial infarction.
BACKGROUND
The pathogenetic mechanism of premature myocardial infarction (MI) remains unknown. We explored the association of homocysteine and its main genetic modulator methylenetetrahydrofolate reductase (MTHFR) 677C->T polymorphism with the development of MI <or=35 years of age.


METHODS
We performed a case-control study of 147 patients with a first MI <or=35 years and 103 age and sex-matched controls. We assessed plasma lipids, homocysteine, folate, vitamin B(12) levels and MTHFR 677C->T polymorphism.


RESULTS
Patients with premature MI had higher homocysteine levels (13.9+/-8.6 vs. 11.8+/-4.9 mmol/l, p=0.02) and higher prevalence of TT homozygocity compared to controls (27.1% vs. 14.6%, p=0.02). Thirty-four patients (23.6%) had angiographically "normal" coronary arteries. Subgroup analysis according to angiographic findings ("normal" coronary arteries versus significant coronary heart disease) showed that only patients with MI and "normal" coronary arteries (MINCA) had higher homocysteine levels compared to controls (17.6+/-12.2 vs. 11.8+/-4.9 mmol/l, p<0.001). The prevalence of TT genotype was higher only in patients with MINCA compared to controls (44.1% vs. 14.6%, p=0.001) (odds ratio 4.6, 95% confidence interval (CI), 1.9-11, p=0.001). This association remained after adjusting for conventional risk factors (odds ratio 3.4, 95% CI, 1.1-10.4, p=0.03). The adjusted odds ratio for MINCA of young individuals with MTHFR TT genotype and folate levels in the lowest quartile (<or=5 ng/ml) was 6.1 (95% CI, 1.1-31, p=0.04).


CONCLUSIONS
Homozygocity for the 677C->T mutation of MTHFR is independently associated with the development of premature MINCA.
Rallidis
Loukianos S
LS
Second Department of Cardiology, University General Hospital, Attikon, Athens, Greece. rallidis@ath.forthnet.gr
Gialeraki
Argiro
A
Komporozos
Christoforos
C
Vavoulis
Panagiotis
P
Pavlakis
Georgios
G
Travlou
Anthi
A
Lekakis
Ioannis
I
Kremastinos
Dimitrios T
DT
D000328:Adult; D016022:Case-Control Studies; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000097:blood; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)