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

J Am Geriatr Soc. 2000 Jun;48(6):664-8. doi: 10.1111/j.1532-5415.2000.tb04725.x.

Abstract

Objective: To determine the association between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and vascular dementia in Ashkenazi 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-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.

Measurements: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / ethnology
  • Alzheimer Disease / genetics
  • Analysis of Variance
  • Case-Control Studies
  • Dementia, Vascular / ethnology*
  • Dementia, Vascular / genetics*
  • Female
  • Gene Frequency
  • Homocysteine / blood
  • Humans
  • Israel / epidemiology
  • Jews / genetics*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Odds Ratio
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Tomography, X-Ray Computed

Substances

  • Homocysteine
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)