Background: The association between methylenetetrahydrofolate reductase (MTHFR) c.677C>T (A222V) polymorphism and Alzheimer's disease (AD) is controversial. The objectives of the study were to investigate the association between MTHFR c.677C>T polymorphism and AD in Korean elders and to the extent to which it is modified by the major components of one-carbon metabolism and apolipoprotein E (APOE) genotype.
Methods: Seven hundred and thirty-two community residents aged 65 or over were clinically assessed for AD. Genotyping was performed for MTHFR c.677C>T and APOE; serum levels of folate, vitamin B(12), and homocysteine were assayed. Age, gender and education were included as covariates.
Results: A trend of association between TT genotype of MTHFR c.677C>T and AD was found [adjusted OR (95% CI): 1.73 (0.80-3.74)]. The association was significant in the presence of below-median vitamin B(12) level [3.66 (1.14-11.71)] and in APOE e4 non-carriers [2.97 (1.00-8.55)] with significant interaction terms, and bordered on significance in the presence of above-median homocysteine level [2.73 (0.94-7.90)].
Conclusions: These findings suggest gene-environment and gene-gene interactions on the risk of AD in Koreans.