DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) including the maintenance enzyme DNMT 1 and de novo methyltransferases DNMT 3a and DNMT 3b. Elevated levels of DNMTs have been found in cancer cells and in several types of human tumors. A polymorphism found in DNMT3b has been associated with increased risk for several cancers. The factors influencing DNMT expression in human tissues have not been clearly determined. he present study examined TDNMT3a and DNMT3b levels in human liver tissue samples and compared the effect of ageing, cigarette smoking, and gender. DNMT3a and DNMT3b expression levels in the samples from older individuals (56-78 years, n = 28) were both significantly higher than those of the younger group (16-48 years, n = 27) (73.2 +/- 3.4 vs 8.3 +/- 2.8 and 56.1 +/- 1.9 vs 17.5 +/- 5.7, respectively; p < 0.05). Levels of DNMT3b in females were significantly higher than those in males (75.4 +/- 2.2 vs 16.3 +/- 4.7; p < 0.05); however, DNMT3a levels were similar for females and males (52.7 +/- 2.7 vs 48.4 +/- 2.0). Expression levels of DNMT3a and DNMT3b were similar in smokers and nonsmokers (58.1 +/- 3.5 vs 60.8 +/- 3.1 and 54.5 +/- 2.3 vs 48.3 +/- 1.8, respectively). Genotyping for DNMT3b (C-->T) variant in this sample pool showed a frequency distribution of CC (41%), CT (50%), and TT (9%). The findings from this study suggest that ageing and gender may be important factors influencing DNA methylation status.
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