Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE?

Background: The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as risk factors for the occurence of Alzheimer's disease (AD) is still controversial: Objective: To verify the association between MTHFR and apolipoprotein E (APOE) polymorph isms and Alzheimer's disease. Method. This work was conducted as a case-control study. Cases included thirty patients with probable AD. Controls were constituted by 29 individuals without dementia according to neuropsychological tests paired to age, sex, race and educational level. DNA was isolated from peripheral leukocytes of anticoagulated venous blood. Genotyping of APOE and MTHFR were performed by DNA amplification and digestion. The frequences of APOE and MTHFR genotypes were submitted by chi-square test corrected by Fisher test; the APOE genotypes, to chi-square linear tendency test and the frequences of MTHFR mutant and AD, by stratificated analysis adjust by Mantel-Haenszel method. Results: There was significant difference about APOE4 and APOE2 in the groups. (p = 0.002) The odds ratio increased exponentially with the increased number of E4 allele (chi(2) linear tendency test). No significant difference was detected on MTHFR genotypes in both case and control groups. Conclusion: The APOE4 is a risk factor and demonstrated a dose-depenent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.