Demethylation of tumor necrosis factor-α converting enzyme promoter associated with high hepatitis B e antigen level in chronic hepatitis B

慢性乙型肝炎患者肿瘤坏死因子-α转换酶启动子去甲基化与乙型肝炎e抗原升高的相关性

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作者:Zhen-Li Wang, Shuai Gao, Xin-You Li, Feng-Kai Sun, Feng Li, Yu-Chen Fan, Kai Wang

Aim

To evaluate tumor necrosis factor-α converting enzyme (TACE) methylation status in patients with chronic hepatitis B (CHB).

Conclusion

Patients with HBeAg-positive CHB have aberrant demethylation of the TACE promoter, which may potentially serve as a biomarker for HBeAg seroconversion.

Methods

Eighty patients with hepatitis B e antigen (HBeAg)-positive CHB, 80 with HBeAg-negative CHB, and 40 healthy controls (HCs) were randomly enrolled in this study. Genomic DNA was extracted from peripheral blood mononuclear cells and methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The clinical and laboratory parameters were collected.

Results

One hundred and thirty of 160 patients with CHB (81.25%) and 38 of 40 HCs (95%) displayed TACE promoter methylation. The difference was significant (χ (2) = 4.501, P < 0.05). TACE promoter methylation frequency in HBeAg-positive CHB (58/80, 72.5%) was significantly lower than that in HBeAg-negative CHB (72/80, 90%; χ (2) = 8.041, P < 0.01) and HCs (χ (2) = 8.438, P < 0.01). However, no significant difference was observed in the methylation frequency between HBeAg-negative CHB and HCs (χ (2) = 0.873, P > 0.05). In the HBeAg-positive group, TACE methylation frequency was significantly negatively correlated with HBeAg (r = -0.602, P < 0.01), alanine aminotransferase (r = -0.461, P < 0.01) and aspartate aminotransferase (r = -0.329, P < 0.01).

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