A mutation in the methylenetetrahydrofolate reductase gene is not associated with increased risk for coronary artery disease or myocardial infarction.
OBJECTIVE
We sought to determine whether the C677T transition in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased risk for coronary artery disease (CAD) or myocardial infarction (MI).


BACKGROUND
Elevated plasma homocysteine has been identified as a risk factor for coronary atherosclerosis. Homocysteinemia may result from deficient MTHFR activity. A thermolabile form of MTHFR, associated with a C677T genetic transition, shows reduced activity and may be a risk factor for CAD.


METHODS
Blood was withdrawn from patients undergoing coronary angiography, and DNA was extracted by a phenol-chloroform method. Genotyping was done by polymerase chain reaction (PCR) amplification of a 198-base pair segment of the MTHFR gene that brackets nucleotide 677. The amplicon was digested with the HinfI restriction enzyme. Products were visualized after electrophoresis in 1.5% agarose with ethidium bromide.


RESULTS
Among 200 patients with a diagnosis of MI, the polymorphic allelic frequency was 33.3%, compared with 32.1% among 554 control subjects (p = 0.68); homozygosity was present in 11.5% of patients and 10.6% of control subjects (p = 0.74, odds ratio [OR] 1.09, 95% confidence interval [CI] 0.63 to 1.82). Among 510 patients with severe CAD (>60% stenosis), allelic frequency was 32.0%, compared with 34.8% for 168 subjects without CAD (<10% stenosis, p = 0.33); 11.2% of patients with CAD compared with 13.1% of control subjects were homozygous (p = 0.50, OR 0.83, 95% CI 0.5 to 1.40).


CONCLUSIONS
Patients with angiographic evidence of CAD or clinical MI do not show an increased frequency of the C677T transition in the MTHFR gene. Our findings do not support this polymorphism as a risk factor for CAD or MI in a predominantly white, well nourished population of unrestricted age.
Anderson
J L
JL
Department of Medicine and Department of Pathology, University of Utah School of Medicine and LDS Hospital, Salt Lake City 84143, USA.
King
G J
GJ
Thomson
M J
MJ
Todd
M
M
Bair
T L
TL
Muhlestein
J B
JB
Carlquist
J F
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003251:Constriction, Pathologic; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005796:Genes; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D017422:Sequence Analysis, DNA
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)