Vitamin B12 is a strong determinant of low methionine synthase activity and DNA hypomethylation in gastrectomized rats

Background/Aims: The respective influence of folate and vitamin B-12 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 B-12 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 B-12. Forty-seven of them underwent total gastrectomy or ileal resection. Results: Low vitamin B-12 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 B-12 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 B-12 was the single determinant of low MTR ( lower quartile, odds ratio = 15.75, p = 0.0017). Low MTR and low vitamin B-12 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). Conclusion: Vitamin B-12 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. Copyright (C) 2003 S. Karger AG, Basel.