Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Jiang DK

PROVIDER: S-EPMC4633722 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Jiang De-Ke DK Ma Xiao-Pin XP Wu Xiaopan X Peng Lijun L Yin Jianhua J Dan Yunjie Y Huang Hui-Xing HX Ding Dong-Lin DL Zhang Lu-Yao LY Shi Zhuqing Z Zhang Pengyin P Yu Hongjie H Sun Jielin J Lilly Zheng S S Deng Guohong G Xu Jianfeng J Liu Ying Y Guo Jinsheng J Cao Guangwen G Yu Long L

Scientific reports 20151105

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 ...[more]

PMID: 26538132

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Project description:BackgroundThough HLA-DP/DQ is regarded to associate with HBV susceptibility and HBV natural clearance, its role in hepatocellular carcinoma (HCC) development is obscure. And the role of STAT4 in HBV susceptibility and clearance as well as HCC development is still contentious. Therefore, we conducted this study, aiming to clarify these obscure relationships.MethodsWe recruited 1312 Chinese Han subjects including healthy controls, HBV carriers and HCC patients in the experiment stage. The meta-analysis included 3467 HCC patients and 5821 HBV carriers to appraise the association with HCC development.ResultsConsistent with previous studies, HLA-DP/DQ associated with HBV susceptibility and HBV natural clearance (p<0.05). However, the experiment showed that HLA-DP rs3077, rs9277535 and rs7453920 did not associate with HCC development (dominant model, rs3077, OR = 0.86, 95%CI = 0.62-1.18; rs9277535, OR = 0.94, 95%CI = 0.68-1.30; rs7453920, OR = 0.75, 95%CI = 0.44-1.27). Meta-analysis again consolidated this conclusion (allele model, rs3077, OR = 0.94, 95%CI = 0.87-1.02; rs9277535, OR = 1.04, 95%CI = 0.97-1.11; rs7453920, OR = 0.89, 95%CI = 0.76-1.02). As for STAT4 rs7574865, we did not find any significant association with HBV susceptibility (OR = 0.91, 95%CI = 0.66-1.26) or HBV natural clearance (OR = 1.13, 95%CI = 0.86-1.49). Moreover, current data failed to acquire positive connection of rs7574865 with HCC development (experiment, OR = 0.86, 95%CI = 0.62-1.19; meta-analysis, OR = 0.87, 95%CI = 0.74-1.03), which may be due to the small sample size.ConclusionsHLA-DP/DQ polymorphisms (rs3077, rs9277535, rs7453920) did not associate with HCC development, but did correlate with HBV susceptibility and HBV natural clearance. STAT4 rs7574865 seemed not to correlate with HBV susceptibility or natural clearance. And it seemed rather ambiguous in its role on HCC development at present.

Dataset Information

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

Publications

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

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