Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction.
BACKGROUND
Elevated plasma homocysteine level is an independent risk factor for cardiovascular disease. A common mutation (nucleotid 677C-T) in the gene coding for methylenetetrahydrofolate reductase (MTHFR) has been reported to reduce the enzymatic activity of MTHFR and is associated with elevated plasma levels of homocysteine, especially in subjects with low folate intake.


OBJECTIVE
Methylenetetrahydrofolate reductase T/T genotype may be a risk factor for premature MI in Turkish population who are known to have low folate levels.


METHODS
The study group was comprised of 96 men (aged <45 years) with premature myocardial infarction (MI) and 100 age- and gender-matched controls who had no history or clinical evidence of coronary artery disease (CAD) and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented.


RESULTS
Allele and genotype frequencies among cases and control subjects were compatible with Hardy-Weinberg equilibrium. The frequencies of T/T, C/T, and C/C genotypes among patients with MI and control subjects were 15.6, 40.6, and 43.8%, and 5, 35, and 60%, respectively. Multivariate analyses identified smoking, MTHFR C/T polymorphism, diabetes mellitus, family history of CAD, and hypertension as the independent predictors of premature MI. Defining patients with non-T/T genotype (C/C and C/T combined) as reference, the relative risk of MI for subjects with T/T genotype was 5.94 (95% confidence interval: 1.96-18.02, p = 0.0016).


CONCLUSIONS
Our findings suggest that C677T transition in the MTHFR gene may be a risk factor for premature MI in Turkish men.
Gülec
S
S
Medical School of Ankara University, Turkey.
Aras
O
O
Akar
E
E
Tutar
E
E
Omürlü
K
K
Avci
F
F
Dinçer
I
I
Akar
N
N
Oral
D
D
D000328:Adult; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000097:blood / Q000235:genetics*; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D014421:Turkey / Q000453:epidemiology
D006710:Homocysteine; D005492:Folic Acid; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)