Abstract
Purpose. ERF3, having been found expressing differently in liver tissues in our previous work, including eRF3a and eRF3b, which are structural homologs named GSPT1 and GSPT2. Recent studies have indicated that eRF3b involved in the development and proliferation of HepG2 cell, and eRF3a may be associated with tumor susceptibility. Based on this, we tested the effects of GSPT1 and GSPT2 single-nucleotide polymorphisms for all major Hepatitis B virus (HBV) outcomes and lamivudine (LAM) treatment in Han Chinese. Method. A total of 1649 samples were enrolled, and peripheral blood samples were collected in the present study. The single-nucleotide polymorphisms in the GSPT1 and GSPT2 region were genotyped using MALDI-TOF MS. Results. Our study demonstrated there was no obvious relevance of either GSPT1-rs33635 or GSPT2-rs974285 polymorphisms with HBV susceptibility, spontaneous recovery, and development of HBV-related diseases. However, we showed for the first time to our knowledge that GSPT1-rs33635C was a predictor for LAM therapy (viral response: odds ratio (OR) = 2.436, P=0.022; biochemical response: OR = 3.328, P=1.73 × 10−4). Conclusions. These findings might provide potential implications for therapeutic guidance.
Highlights
Hepatitis B virus (HBV) infection has become a major global health problem with a total of approximately 350 million chronic carriers distributed worldwide [1]
Experimental results have revealed a series of genes potentially associated with HBV-related diseases and the outcome of treatment: including TNF, PDCD1, CTLA-4, transforming growth factor (TGF)-α, and CXCL-10 were associated with persistent HBV infection [7–12], our previous study indicated that HLA, PAPL, IL10RB, and DEPDC5 loci were associated with both HBV-related diseases and HBV clearance, and HLA allele polymorphism had relevance with the outcomes of lamivudine (LAM) treatment [13,14]
After adjustment for gender, age, smoking, alcohol, HBV DNA, and HbeAg (+/−), there was an association of rs33635C with the viral response in the codominant genetic models
Summary
Hepatitis B virus (HBV) infection has become a major global health problem with a total of approximately 350 million chronic carriers distributed worldwide [1]. The clinical outcome of the infection varies widely and may include natural clearance (NC), chronic hepatitis, HBV-related liver cirrhosis (LC), or hepatocellular carcinoma (HCC) [3,4]. Our research showed that eRF3a/GSPT1 and eRF3b/GSPT2 were positively expressed in liver tissues. We considered eRF3b/GSPT2 is probably associated with the development of HBV-related liver disease. In recent years, studies have found that eRF3a may be associated with tumor susceptibility [16–18]. It is not understood whether GSPT1 and GSPT2 polymorphism is relevant to HBV infection and prognosis upon therapeutic intervention in Chinese people. Further investigation was carried out for testing the relevance of the GSPT1 and GSPT2 polymorphisms with prognosis after therapy with LAM
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