Abstract
Tumor necrosis factor receptor superfamily 2 (TNFR2) plays an important role in controlling the progression of antiviral and antitumorr. Evidence suggests that TNFR2 is involved in the pathogenesis of HBV-induced liver injury. We therefore examined whether TNFR2 polymorphisms are associated with the risk of HBV-related liver disease in Chinese population. In this case-control study, 115 chronic hepatitis B (CHB) patients, 86 HBV-related liver cirrhosis patients (LC), 272 HBV-related hepatocellular carcinoma patients (HCC) and 269 healthy controls were recruited. TNFR2 rs1061622 and rs1061624 polymorphisms were examined using a polymerase chain reaction-restriction fragment length polymorphism analysis. Binary logistic regression analyses revealed that the A allele of rs1061624 was positively associated with the risk of CHB (AA vs. GG, P = 0.026; AA vs. GA+GG, P = 0.021), LC (AA vs. GG, P = 0.027; AA+GA vs. GG, P = 0.036), and HCC (GA vs. GG, P = 0.046; GA+AA vs. GG, P = 0.031). Moreover, subgroup analysis indicated that male subjects have increased risk in developing CHB and LC. Nevertheless, no association was found between rs1061622 polymorphism and HBV-related liver diseases in the overall or subgroup analyses. Our retrospective study suggests that the TNFR2 rs1061624 polymorphism is associated with HBV-related CHB, LC, and HCC in Chinese population, particularly in males.
Highlights
hepatocellular carcinoma (HCC) is a complex and multifactorial process
As compared with the control group, the three case groups (CHB, liver cirrhosis (LC), and HCC) have statistically different laboratory results for sex, age, and ethnicity (P < 0.05), the chronic hepatitis B (CHB) group had a higher proportion of alcohol drinkers, and the LC group had a higher proportion of smokers
We performed a logistic regression analysis and found that there was a significant association between Tumor necrosis factor receptor superfamily 2 (TNFR2) rs1061624 polymorphism and CHB susceptibility in the additive model (AA vs. GG) and the recessive model (AA vs. GA+GG), with adjusted odds ratio (OR) of 2.666 and 2.459, respectively
Summary
HCC is a complex and multifactorial process. Environmental factors such as exposure to aflatoxin, excess intake of alcohol, liver cirrhosis, and infections with the hepatitis B virus (HBV) or hepatitis C virus (HCV) have been associated with its development. Tumor necrosis factor alpha (TNF-α), a multifunctional cytokine, has a great influence on host immune response to HBV/HCV infection and the pathogenesis of autoimmune and malignant diseases[8,9]. It has been implicated in the pathophysiology of liver cancer[10]. TNFR2 gene polymorphism has been associated with a susceptibility to and the progression of various cancers Such observations have increased our interest in examining the impact of the TNFR2 196 M/R genotype on liver carcinogenesis. Differences in genotype frequency between the chronic hepatitis (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) cases and healthy controls were examined
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