Abstract
Background: Two common functional polymorphisms in the promoter region of TNF-α located at nucleotides -238 (rs361525) and -308 (rs1800629) have been reported to regulate the expression of tumour necrosis factor alpha (TNF-α) and to be associated with hepatitis B virus (HBV) infection related diseases. However, their frequencies and associations with outcomes of HBV infection are not clear.
Methods: We performed a genetic analysis of 956 Chinese Han subjects, who were divided into a HBV clearance group, an asymptomatic persistent infection group, a chronic hepatitis B group, two stages of liver cirrhosis (LC) groups, and three stages of hepatocellular carcinoma (HCC) groups to examine the relationship among HBV infection related diseases and these two single nucleotide polymorphisms (SNPs).
Results: The phenotype of polymorphism -238 in all study samples displayed no significant differences among the eight subgroups. The distribution of -308 phenotypes among the eight groups differed significantly. For females, compared with persistent infection, LC patients had a significantly higher A allele frequency, and the association with cirrhosis progression was significant. For males, there were statistically significant differences in allele distributions between the persistent infection group and the HCC group. The AG haplotype (-A308, -G238) was associated significantly with HCC development.
Conclusions: The results of the present study indicate an association between rs1800629 and HBV related disease progression in the Chinese Han population. The association was different between genders, with the rs1800629 A allele being a risk factor for female carriers to develop LC, and the allele being a risk factor for male carriers to develop HCC, especially in subjects with an alcohol abuse or cigarette smoking history.
Acknowledgements:
This work was supported by the National Science and Technology Pillar Program of China (No. 2008BAH24B05) and the National Infrastructure Program of Chinese Genetic Resources (2006DKA21300). ZZ was supported for this project by both the National Nature Science Foundation of China (No. 30671855) and the National Cancer Institute, National Institute of Health, USA, under Contract No. N01-CO-12400. The content of this publication does not necessarily reflect the views or the policies of the Department of Health and Human Service, nor does mention of trade names, commercial products or organisations imply endorsement by the US Government.
Members of the HBV Study Consortium are as follows: Department of Infectious Diseases, Peking University First Hospital, Beijing, (Zheng Zeng, Yanyan Yu, Xiaoyuan Xu, Haiying Lu); Institute of Liver Diseases Research, Beijing Military General Hospital, Beijing, (Darong Hu); Beijing Ditan Hospital (Rongbing Wang); Department of Surgery, Beijing Institute of Tumor Prevention and Therapy, Beijing, (Cunyi Hao); Department of Infectious Diseases, Shanxi Medical University, Taiyuan, (Heping Zhou); Department of Infectious Diseases, Qinhuangdao No. 3 Hospital, Qinhuangdao, (Zhonghou Han); Department of Surgery, Inner Mongolia Medical College, Hohhot, (Lidao Bao, Xiping Zhang); Department of Infectious Diseases, Xuzhou No. 3 Hospital, Xuzhou, (Dasi Guo); Department of Infectious Diseases, Xinjian Medical University, Urumoqi, (Yaoxin Zhang); Department of Infectious Diseases, the Second Affiliate Hospital of China Medical University, Shenyang, (Xiaoguang Dou); Institute of Liver Diseases Research, Peking University Second Hospital, Beijing, (Lai Wei); Department of Surgery, Peking Union Medical College, Beijing, (Jingan Rui, Qiang Qu), Peoples Republic of China.