Research Article

Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels

Published: October 29, 2013
Genet. Mol. Res. 12 (4) : 5160-5171 DOI: 10.4238/2013.October.29.10

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

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