The methylenetetrahydrofolate reductase C677T polymorphism does not associate with susceptibility to abdominal aortic aneurysm.
OBJECTIVE
To test whether the T variant of the C677T polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) would associate with three distinct forms of vascular disease, abdominal aortic aneurysm (AAA), coronary artery disease (CAD) and peripheral vascular disease (PVD).


BACKGROUND
Increases in homocysteine induce elastolytic activity in the arterial wall, a condition which may favour vascular pathogenesis including aneurysm formation. Homozygosity of the common T variant of the C677T polymorphism in the gene for MTHFR has been shown to associate with increased levels of homocysteine. Thus, this functional polymorphism may lead to an increased propensity to develop cardiovascular disease and, in particular, AAA.


METHODS
An association study was conducted across 1207 subjects; 428 patients with AAA, 271 CAD patients, 226 PVD patients and 282 controls being genotyped for the C667T variants of MTHFR.


RESULTS
There were no significant differences in the frequency of the MTHFR C677T variant between any of the groups examined. AAA patients who were homozygotes for the 677T allele did, however, appear to have significantly larger aneurysms than C allele carriers.


CONCLUSIONS
This study provides no evidence that the T variant of MTHFR is associated with susceptibility to AAA, CAD or PVD. It may, however, be a contributory factor in AAA severity as indicated by aneurysm size.
Department of Surgery, Dunedin School of Medicine, Otago University, Dunedin, New Zealand. greg.jones@otago.ac.nz
G T
GT
Jones
E L
EL
Harris
L V
LV
Phillips
A M
AM
van Rij
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index
D042965:Methylenetetrahydrofolate Reductase (NADPH2)