Folate, homocysteine, vitamin B12, and polymorphisms of genes participating in one-carbon metabolism in late-onset Alzheimer's disease patients and healthy controls.
OBJECTIVE
We screened 378 late-onset Alzheimer's disease (LOAD) patients and 308 matched controls for the presence of the common MTHFR 677C>T, MTRR 66A>G, MTR 2756 A>G, and TYMS 28 bp repeat polymorphisms, searching for association with disease risk and age at onset. Moreover, we searched for correlation between each of the studied polymorphisms and available data on plasma homocysteine (Hcy), serum folate, and vitamin B12 values.


RESULTS
We observed a significant increased frequency of the MTHFR 677T allele (0.48 vs. 0.42; p=0.019) and of MTHFR 677CT (OR=1.46; 95%CI=1.03-2.06) and TT genotypes (OR=1.62; 95%CI=1.05-2.49) in LOAD subjects with respect to controls. We also observed a significant increased frequency of the MTRR 66G allele (0.49 vs. 0.43; p=0.044) and of the MTRR 66GG genotype (OR=1.57; 95%CI=1.01-2.46) in the LOAD group. Significantly increased mean plasma Hcy levels (22.7±1.7 vs 14.5±1.7 μmol/L; p=0.037) and decreased serum folate values (5.7±0.5 vs. 7.8±0.8 ng/mL; p=0.005) were observed in LOAD subjects with respect to controls, whilst the difference in serum vitamin B12 values did not reach statistical significance. Several interactions between the studied polymorphisms and biochemical biomarkers were observed. None of the studied polymorphisms was associated with disease age at onset.


METHODS
The present study suggests that the MTRR 66G allele might contribute to LOAD risk and confirms an increased frequency of the MTHFR 677T allele in LOAD.


CONCLUSIONS
Overall, present results support a contribution for one-carbon metabolism to LOAD pathogenesis.
Faculty of Medicine, University of Pisa, Pisa, Italy. f.coppede@geog.unipi.it
Fabio
F
Coppedè
Pierpaola
P
Tannorella
Ilaria
I
Pezzini
Francesca
F
Migheli
Giulia
G
Ricci
Elena
E
Caldarazzo lenco
Irene
I
Piaceri
Antonio
A
Polini
Benedetta
B
Nacmias
Fabio
F
Monzani
Sandro
S
Sorbi
Gabriele
G
Siciliano
Lucia
L
Migliore
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000378:metabolism; D005838:Genotype; D006262:Health; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D014805:Vitamin B 12 / Q000097:blood* / Q000378:metabolism
D015415:Biomarkers; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12