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Sci Rep. 2015 Nov 5;5:16278. doi: 10.1038/srep16278.

Genetic variations in STAT4,C2,HLA-DRB1 and HLA-DQ associated with risk of hepatitis B virus-related liver cirrhosis.

Jiang DK1,2,3,4,5,6, Ma XP1, Wu X7, Peng L8, Yin J9, Dan Y10, Huang HX1, Ding DL1, Zhang LY1, Shi Z1,2,3,4, Zhang P1,2,3,4, Yu H1,2,3,4, Sun J5, Lilly Zheng S5,6, Deng G10, Xu J1,2,3,4,5,6,11, Liu Y7, Guo J8, Cao G9, Yu L1,12.

Author information

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Center for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China.
Center for Genetic Translational Medicine and Prevention, Fudan University, Shanghai, China.
Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Program for Personalized Cancer Care, NorthShore University HealthSystem, the University of Chicago, IL, USA.
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Division of Digestive Diseases, Zhongshan Hospital, Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Department of Infectious Diseases, Southwest Hospital, Institute of Immunology, Third Military Medical University, and Chongqing Key Laboratory of Infectious Diseases, Chongqing, China.
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Institute of Biomedical Science, Fudan University, Shanghai, China.


Recent genome-wide associated studies (GWASs) have revealed several common loci associated with the risk of hepatitis B virus (HBV)- or hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We selected 15 single nucleotide polymorphisms (SNPs) identified through GWASs on HBV- or HCV-related HCC, and genotyped them in two independent Chinese cohorts of chronic HBV carriers, including 712 LC cases and 2601 controls. The association of each SNP with the risk of HBV-related LC was assessed by meta-analysis of the two cohorts. Of the 12 SNPs reported in HBV-related HCC GWASs, five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA-DQ), were found to be significantly associated with the risk of HBV-related LC (rs7574865: P = 1.79 × 10(-2), OR = 1.17, 95% CI = 1.03-1.34; rs9267673: P = 4.91 × 10(-4), OR = 1.37, 95% CI = 1.15-1.63; rs2647073: P = 3.53 × 10(-5), OR = 1.63, 95% CI = 1.29-2.06; rs3997872: P = 4.22 × 10(-4), OR = 1.86, 95% CI = 1.32-2.62; rs9275319: P = 1.30 × 10(-2), OR = 1.32, 95% CI = 1.06-1.64). However, among the three SNPs associated with the risk of HCV-related HCC in previous GWASs, none of them showed significant association with the risk of HBV-related LC. Our results suggested that genetic variants associated with HBV-related hepatocarcinogenesis may already play an important role in the progression from CHB to LC.

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