Associations of methylenetetrahydrofolate reductase C677T polymorphism with markers of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study.
OBJECTIVE
To study whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism or serum homocysteine concentration is associated with carotid artery intima media thickness (IMT), carotid artery compliance (CAC) or brachial artery flow mediated dilatation (FMD) in a healthy Finnish adult population.


METHODS
Cross-sectional data obtained in 2001 for the Cardiovascular Risk in Young Finns Study were used. Carotid artery IMT, CAC and brachial FMD were measured by ultrasound and serum homocysteine concentrations using a commercial immunoassay kit. We studied 1,440 subjects (aged 24-39 years). Genotyping was performed using the 5' nuclease TaqMan assay.


RESULTS
Homocysteine values differed between genotypes in women and men (ANOVA, p<0.001 for both sex groups): the genotype raised values in the order of CC, CT, TT. There was a significant difference in CAC values between the MTHFR genotypes in men (ANOVA, p = 0.008), and the CC genotype had the lowest values. In multivariate linear regression analysis adjusted for other major coronary risk factors (e.g. age, smoking, body mass index, systolic blood pressure, C-reactive protein), the association remained significant (R (2) = 25.8 %, beta = 0.091; p = 0.02). Homocysteine level was directly associated with CAC in the whole population (R (2) = 18.0 %, beta = 0.012; p = 0.014) and in women (R (2) = 9.3%, beta = 0.02; p = 0.013), but not in men (R (2) = 15.2 %, beta = 0.004; p = 0.444). We found no association between homocysteine level or the MTHFR polymorphism and carotid IMT or brachial artery FMD.


CONCLUSIONS
The findings suggest that the MTHFR polymorphism does not influence IMT or FMD, but that the T allele may have an effect on CAC in men.
Collings
A
A
Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, and Medical School at the University of Tampere, Finland. auni.collings@pshp.fi
Raitakari
O T
OT
Juonala
M
M
Rontu
R
R
Kähönen
M
M
Hutri-Kähönen
N
N
Rönnemaa
T
T
Marniemi
J
J
Viikari
J S A
JS
Lehtimäki
T
T
D000328:Adult; D000367:Age Factors; D016632:Apolipoprotein A-I / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D015992:Body Mass Index; D001916:Brachial Artery / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005387:Finland; D005787:Gene Frequency; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation
D016632:Apolipoprotein A-I; D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)