Methylenetetrahydrofolate reductase genotypes and early-onset coronary artery disease.
BACKGROUND
Homozygosity for the common (677C-->T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with hyperhomocysteinemia, but there is uncertainty as to the association between this mutation and coronary artery disease (CAD). This study examined the association between MTHFR genotypes and age at onset of CAD.


RESULTS
Patients (n=169) with documented myocardial infarction or angiographically documented CAD who were aged < or = 55 years at onset of CAD symptoms and DNA samples from control subjects (n=313) were studied. The prevalence of homozygosity among patients with early CAD onset (aged < or = 45 years) was 28%, which was significantly higher than that in patients with later onset (13%) and in control subjects (14%) (odds ratio 2.4, 95% CI 1.24 to 4.69, P=0.006, and odds ratio 2.7, 95% CI 1.15 to 6.42, P=0.01, respectively). Plasma folate was lower in TT homozygotes who had early CAD onset than in those with later onset (P=0.005). Among patients with plasma folate in the lowest quintile (< or = 12.6 nmol/L), 31% were homozygotes, as were 45% of those with low plasma folate and early CAD onset. There was no difference in the prevalence of traditional risk factors among genotypes. The frequency of homozygosity in patients with < or = 1 risk factor was higher than in those with > or = 2 risk factors (30% versus 12%, P<0.05). In multiple regression analysis, TT homozygosity and plasma folate were independently associated with CAD, but the impact of folate was small.


CONCLUSIONS
Homozygosity for the 677C-->T mutation of MTHFR is common and is associated with an increased risk of premature CAD in this population.
Mager
A
A
Department of Cardiology, Rabin Medical Center, Beilinson Campus, Petah-Tiqva, and The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Lalezari
S
S
Shohat
T
T
Birnbaum
Y
Y
Adler
Y
Y
Magal
N
N
Shohat
M
M
D017668:Age of Onset; D000483:Alleles; D003327:Coronary Disease / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors
D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)