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 occurrence of Alzheimer's disease (AD) is still controversial.


OBJECTIVE
To verify the association between MTHFR and apolipoprotein E (APOE) polymorphisms and Alzheimer's disease.


METHODS
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 (chi2 linear tendency test). No significant difference was detected on MTHFR genotypes in both case and control groups.


CONCLUSIONS
The APOE4 is a risk factor and demonstrated a dose-dependent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.
Fernandez
Liana Lisboa
LL
Biomedical Geronthology Institute, PUCRS, Porto Alegre, RS, Brazil.
Scheibe
Rosane Machado
RM
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005819:Genetic Markers; D042965:Methylenetetrahydrofolate Reductase (NADPH2)