Relation of a common mutation in methylenetetrahydrofolate reductase to plasma homocysteine and early onset coronary artery disease.
OBJECTIVE
In the presence of low serum folate, mutant 5,20-methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life.


METHODS
Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group.


RESULTS
There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01).


CONCLUSIONS
The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.
Dunn
J
J
Department of Pathology, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada.
Title
L M
LM
Bata
I
I
Johnstone
D E
DE
Kirkland
S A
SA
O'Neill
B J
BJ
Zayed
E
E
MacDonald
M C
MC
Dempsey
G
G
Nassar
B
B
D017668:Age of Onset; D000368:Aged; D001322:Autoanalysis; D002851:Chromatography, High Pressure Liquid; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D004198:Disease Susceptibility; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006720:Homozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)