Homocysteine and methylenetetrahydrofolate reductase polymorphism in Alzheimer's disease.

Homocysteine metabolism is influenced by genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR 677 C-->T and 1298 A-->C) and transcobalamin genes (TCN1 776 C-->G ). We evaluated the association of homocysteine with Alzheimer's disease (AD) and the influence of related polymorphisms and APOE, in 180 cases and 181 controls from southern Italy. Homocysteine (upper tercile) was associated with AD risk, with an odds ratio of 2.8 (95% confidence interval (CI) 1.54-5.22, p=0.0008), which was increased 2.2- and 2.0-fold by MTHFR 677T (odds ratio 6.28, 95% CI 2.88-16.20, p < 0.0001) and APOE epsilon4 (odds ratio: 5.60, 95% CI 1.12-28.05, p=0.0361), respectively. In conclusion, association of homocysteine with AD was aggravated by MTHFR 677T and APOE epsilon4 alleles.