Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels.
Genet Mol Res
; 12(4): 5160-71, 2013 Oct 29.
Article
em En
| MEDLINE
| ID: mdl-24301776
ABSTRACT
Hypomethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter in glioma cells has been associated with temozolomide resistance. S-adenosylmethionine (SAM), which is produced during folate metabolism, is the main source of methyl groups during DNA methylation. As a key enzyme during folate metabolism, polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) may regulate folate end-products. We investigated the effect of typical polymorphisms of MTHFR (C677T and A1298C) on MGMT methylation based on different serum folate levels in patients with glioma from Northeast China. A total of 275 patients with glioma and 329 without malignant tumors were tested. Serum folate concentration was assayed by using the electrochemiluminescence immunoassay. MTHFR polymorphisms were detected by Taqman-Fluorescence quantitative polymerase chain reaction (PCR). Methylation-specific PCR was used to assess MGMT methylation. The constituent ratio of glioma patients below the serum folate biological reference value was significantly higher than that of the control population (P < 0.001). In patients with oligodendroglioma and glioblastoma, heterozygotes for the A1298C mutation were found in higher frequency than homozygotes or wild types (oligodendroglioma, P < 0.001; glioblastoma, P < 0.01). When grouped by the median or biological reference value of serum folate, only homozygotes for C677T with low levels of folate were significantly associated with decreased methylation of MGMT (median, P < 0.001; biological reference value, P = 0.036). These data suggest that, in combination with a negative folate balance in glioma patients, T/T genotypes in MTHFR C677T may be associated with MGMT demethylation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Metilases de Modificação do DNA
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Metilação de DNA
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Proteínas Supressoras de Tumor
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Enzimas Reparadoras do DNA
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Metilenotetra-Hidrofolato Redutase (NADPH2)
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Ácido Fólico
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Glioma
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article