The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and vascular dementia.
OBJECTIVE
To determine the association between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and vascular dementia in Ashkenazi and non-Ashkenazi Jews.


METHODS
A case-control study.


METHODS
Nursing homes in Jerusalem, Israel.


METHODS
Two hundred fifty nine Jewish people of Ashkenazi and non-Ashkenazi origin, older than age 70, who have vascular dementia (VD) (n = 85), Alzheimer's disease (AD) (n = 92), and who are cognitively intact (n = 82) with no clinical evidence of atherosclerotic vascular disease.


METHODS
The frequencies of the mutant allele (T allele) and homozygotes for the C677T MTHFR mutation (T/T genotype). The total plasma homocysteine (tHCT) level in 75 subjects.


RESULTS
There were no significant differences in the frequencies of the T/T genotype or T allele among VD, AD, and cognitively intact older people of the same ethnic origin (0.15, 0.19, 0.25 T/T genotype and 0.42, 0.46, 0.47 T allele in Ashkenazi; 0.08, 0.06, 0.10 T/T genotype and 0.28, 0.32, 0.33 T allele in non-Ashkenazi with VD and AD, and in cognitively intact older people, respectively). The relative risk of VD associated with the T/T genotype versus the C/C genotype was 0.62 (95% CI, 0.19-1.19) in Ashkenazi and 0.65 (95% CI, 0.11-3.7) in non-Ashkenazi, respectively. The relative risk of AD associated with the T/T genotype was 0.85 (95% CI, 0.29-2.45) in Ashkenazi and 0.62 (95% CI, 0.1-4.3) in non-Ashkenazi, respectively. The frequencies of mutant homozygotes and allele were significantly higher in Ashkenazi than in non-Ashkenazi Jews (19.9% vs 7.5% T/T genotype, chi2 = 6.2, P = .01, 0.45 vs 0.31 T allele, chi2 = 9.77, P = .002 in Ashkenazi vs non-Ashkenazi, respectively). There were no differences in mean tHCT concentration among VD, AD, and cognitively intact older people.


CONCLUSIONS
The MTHFR C677T is not associated with an increased risk of vascular dementia or Alzheimer's disease. The frequency of the mutation is significantly higher in Ashkenazi compared with non-Ashkenazi Jews.
Pollak
R D
RD
Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Pollak
A
A
Idelson
M
M
Bejarano-Achache
I
I
Doron
D
D
Blumenfeld
A
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics; D000704:Analysis of Variance; D016022:Case-Control Studies; D015140:Dementia, Vascular / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014057:Tomography, X-Ray Computed
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)