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Abstract
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.
Highlights
Hepatitis B virus (HBV) infection is one of the major causes of chronic hepatitis and the main risk factor for liver cirrhosis and hepatocellular carcinoma (HCC) [1]
These findings were validated by many a study [6,7,8,9,10], especially in Asians, like Chinese Han, Japanese, Korean and so on. Hu and his colleagues [7] first pointed out that HLA-DP/DQ associated with HBV clearance, and correlated with HCC development, with HLA-DQ rs2856718 significantly decreasing HCC risk and rs3077 an approaching significant effect on HCC development. In their further research [11], they found additional HLA-DQ single nucleotide polymorphism (SNP) rs9272105 correlated with HCC development, when they validated the previous SNPs, they only found rs9277535 pertained to HCC development, which was regarded as insignificant in their previous study [7], vice versa, the previous proved-tobe significant SNPs did not reach statistical significance again
In this study, we mainly aimed to investigate the association of HLA-DP rs3077, rs9277535, HLA-DQ rs7453920 and Signal Transducer and Activator of Transcription 4 (STAT4) rs7574865 with HCC development, chronicity of HBV infection in Han population dwelling in West China, both from experiment and meta-analysis perspective to clarify the currently ambiguous role of these SNPs with HCC development, and to validate their correlations with HBV susceptibility and clearance from the experiment
Summary
Hepatitis B virus (HBV) infection is one of the major causes of chronic hepatitis and the main risk factor for liver cirrhosis and hepatocellular carcinoma (HCC) [1]. Recent Genome-Wide Association studies (GWAS) revealed that HLA-DP/DQ polymorphisms (HLA-DP rs3077, rs9277535, HLA-DQ rs2856718, rs7453920) associated with HBV clearance [4,5], from a genetic perspective to investigate the etiology of chronic hepatitis B. These findings were validated by many a study [6,7,8,9,10], especially in Asians, like Chinese Han, Japanese, Korean and so on. We conducted this study, aiming to clarify these obscure relationships
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