Methylation of the Glutathione-S-Transferase M3 Gene Promoter is Associated with Oxidative Stress in Acute-on-Chronic Hepatitis B Liver Failure

Methylation of the Glutathione-S-Transferase M3 Gene Promoter is Associated with Oxidative Stress in Acute-on-Chronic Hepatitis B Liver Failure

LI QI,^1,2 ZHI-QIANG ZOU,³ LI-YUAN WANG,¹ SHUAI GAO,¹ YU-CHEN FAN,^1,2 BO LONG,³ YAN-MEI GUO,³ AI-LING XU,³ JIE HAN,¹ TAO LI¹ and KAI WANG^1,2

¹Department of Hepatology, Qilu Hospital of Shandong University, Jinan, P.R. China
²Institute of Hepatology, Shandong University, Jinan, P.R. China
³Department of Hepatology, Yantai Infectious Disease Hospital, Yantai, P.R. China

Chronic hepatitis B (CHB) is a major cause for liver disease worldwide, ranking as the first cause for liver cirrhosis and hepatocellular carcinoma. Acute-on-chronic hepatitis B liver failure (ACHBLF) is most commonly caused by acute severe exacerbation during CHB virus infection. The pathophysiology of ACHBLF is still poorly understood. Glutathione-S-transferase (GST) M3 belongs to GSTs superfamily and it has been demonstrated to contribute to oxidative stress-mediated liver damage. The present study was aimed to determine the potential association between GSTM3 promoter methylation and oxidative stress in ACHBLF patients. Thirty ACHBLF patients, 30 CHB patients and 10 healthy controls were included in this study. Methylation of GSTM3 promoter was determined using methylation-specific PCR (MSP) method. Plasma biomarkers for oxidative stress including malondialdehyde (MDA) and GST were detected by enzyme-linked immunosorbent assay (ELISA). Model for end-stage liver disease (MELD) scoring system was used for predicting the severity and prognosis of liver failure. ACHBLF patients had significant higher GSTM3 promoter methylation rate than CHB patients (30% versus 6.7%, χ² = 5.455, P = 0.020). Plasma MDA and GST levels were significantly increased in ACHBLF patients compared with CHB patients. Meanwhile, MDA, MELD scores and mortality rate were significantly higher in methylated group than those in unmethylated group of ACHBLF patients. Furthermore, plasma MDA levels were positively correlated with MELD scores of ACHBLF (r = 0.588, P = 0.001). In conclusion, the methylation of GSTM3 promoter may contribute to oxidative stress-associated liver damage and correlate with the disease severity in ACHBLF.

keywords —— acute-on-chronic hepatitis B liver failure; glutathione-S-transferase; malondialdehyde; oxidative stress; promoter methylation

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Tohoku J. Exp. Med., 2012, 228, 43-51

Correspondence: Kai Wang, M.D., Ph.D., Department of Hepatology, Qilu Hospital of Shandong University and Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan 250012, P.R. China.

e-mail: wangdoc876@126.com, wangdoc876@yahoo.com.cn