IL28B Is Associated with Outcomes of Chronic HBV Infection.
10.3349/ymj.2015.56.3.625
- Author:
Xiaodong SHI
1
;
Xiumei CHI
;
Yu PAN
;
Yanhang GAO
;
Wanyu LI
;
Chen YANG
;
Jin ZHONG
;
Damo XU
;
Manna ZHANG
;
Gerald MINUK
;
Jing JIANG
;
Junqi NIU
Author Information
1. Department of Hepatology, First Hospital of Jilin University, Changchun, China. junqiniu2013@aliyun.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Hepatitis B virus;
interleukin 28B;
cirrhosis;
hepatocellular carcinoma;
genetic variation
- MeSH:
Adult;
Aged;
Alanine Transaminase/blood;
Asian Continental Ancestry Group/*genetics;
Biological Markers/blood;
Carcinoma, Hepatocellular/genetics;
Case-Control Studies;
China;
DNA, Viral/blood;
Enzyme-Linked Immunosorbent Assay;
Female;
Genotype;
Hepatitis B virus/genetics;
Hepatitis B, Chronic/ethnology/*genetics/immunology/*virology;
Humans;
Interleukins/blood/*genetics/metabolism;
Leukocytes, Mononuclear;
Liver Cirrhosis/blood;
Liver Neoplasms/genetics;
Male;
Middle Aged;
RNA, Messenger/*genetics;
Reverse Transcriptase Polymerase Chain Reaction
- From:Yonsei Medical Journal
2015;56(3):625-633
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
