1.IL28B Is Associated with Outcomes of Chronic HBV Infection.
Xiaodong SHI ; Xiumei CHI ; Yu PAN ; Yanhang GAO ; Wanyu LI ; Chen YANG ; Jin ZHONG ; Damo XU ; Manna ZHANG ; Gerald MINUK ; Jing JIANG ; Junqi NIU
Yonsei Medical Journal 2015;56(3):625-633
PURPOSE: The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. MATERIALS AND METHODS: IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. RESULTS: Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). CONCLUSION: Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.
Adult
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Aged
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Alanine Transaminase/blood
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Asian Continental Ancestry Group/*genetics
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Biological Markers/blood
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Carcinoma, Hepatocellular/genetics
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Case-Control Studies
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China
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DNA, Viral/blood
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Enzyme-Linked Immunosorbent Assay
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Female
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Genotype
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Hepatitis B virus/genetics
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Hepatitis B, Chronic/ethnology/*genetics/immunology/*virology
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Humans
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Interleukins/blood/*genetics/metabolism
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Leukocytes, Mononuclear
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Liver Cirrhosis/blood
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Liver Neoplasms/genetics
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Male
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Middle Aged
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RNA, Messenger/*genetics
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Reverse Transcriptase Polymerase Chain Reaction