Vitamin B12 is a strong determinant of low methionine synthase activity and DNA hypomethylation in gastrectomized rats.
OBJECTIVE
The respective influence of folate and vitamin B12 deficiency on MTR activity and transcription, and on DNA methylation is not clearly established. The aim of this study was to assess the respective influence of folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA methylation.


METHODS
Sixty-one rats were administered normal diet or diet deficient in choline, methionine, folic acid and vitamin B12. Forty-seven of them underwent total gastrectomy or ileal resection.


RESULTS
Low vitamin B12 was observed only in gastrectomized rats. Low folate was observed in rats under deficient diet. Total MTR activity (holo- + apoenzyme) was lowered only with vitamin B12 level <200 pmol/l (p=0.0002), while the ratios of total vs. holo-MTR activity and of transcripts MTR vs. GAPDH (RT-PCR) were unchanged. Vitamin B12 was the single determinant of low MTR (lower quartile, odds ratio=15.75, p=0.0017). Low MTR and low vitamin B12 were the two determinants of DNA hypomethylation (lower quartile) (odds ratio=17.07, p=0.0006, and odds ratio=7.31, p=0.006, respectively).


CONCLUSIONS
Vitamin B12 affects MTR expression by a non-transcriptional mechanism different from a protective effect on MTR proteolysis. It is also a strong determinant of DNA hypomethylation.
Brunaud
Laurent
L
Cellular and Molecular Pathology in Nutrition, EMI, INSERM 0014, URM IFREMER 20, CHU Nancy-Brabois, Vandoeuvre-lès-Nancy, Nancy, France.
Alberto
Jean-Marc
JM
Ayav
Ahmet
A
Gérard
Philippe
P
Namour
Farès
F
Antunes
Laurent
L
Braun
Marc
M
Bronowicki
Jean-Pierre
JP
Bresler
Laurent
L
Guéant
Jean-Louis
JL
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism*; D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D005494:Folic Acid Deficiency / Q000503:physiopathology; D005743:Gastrectomy; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014806:Vitamin B 12 Deficiency / Q000503:physiopathology*
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase