The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) geneand vascular dementia

OBJECTIVE: To determine the association between the C677T mutation in the m ethylenetetrahydrofolate reductase (MTHFR) gene and vascular dementia in As hkenazi and non-Ashkenazi Jews. DESIGN: A case-control study. SETTING: Nursing homes in Jerusalem, Israel. PARTICIPANTS: Two hundred fifty nine Jewish people of Ashkenazi and non-Ash kenazi 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. MEASUREMENTS: The frequencies of the mutant allele (T allele) and homozygot es for the C677T MTHFR mutation (T/T genotype). The total plasma homocystei ne (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 p eople, respectively). The relative risk of VD associated with the T/T genot ype versus the C/C genotype was 0.62 (95% CI, 0.19-1.19) in Ashkenazi and 0 .65 (95% CT, 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 Ashken azi and 0.62 (95% CI, 0.1-4.3) in non-Ashkenazi, respectively. The frequenc ies of mutant homozygotes and allele were significantly higher in Ashkenazi than in non-Ashkenazi Jews (19.9% vs 7.5% TIT genotype, chi(2) = 6.2, P = .01, 0.45 vs 0.31 T allele, chi(2) = 9.77, P = .002 in Ashkenazi vs non-Ash kenazi, 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 va scular dementia or Alzheimer's disease. The frequency of the mutation is si gnificantly higher in Ashkenazi compared with non-Ashkenazi Jews.