Associations Of Single Nucleotide Polymorphisms Of 3'UTR HLA-DPA1 With Chronic Hepatitis B Virus Infection And Hepatocellular Carcinoma

[Background and aims]:As an important gene group for immune response,Human leukocyte antigen (HLA) may play a key role in HBV infection and the occurrence of HCC. The different susceptibility to disease of HLA depends on its wealth genetic polymorphism, especially the polymorphism of HLA classâ…¡. A recently genomewide association study in Japanese and Thai populations has found an association between the risk of developing chronic hepatitis B virus (HBV) infection and rs3077, which lies in the 3'untranslated region (3'UTR) of HLA-DPA1. We thus validate the results in the Chinese population. In addition, a further study of the relationship between the rs3077 and different outcomes of the HBV infection, as well as the the occurrence of HCC, was carred out, and we also try to explore its possible mechanism.[Methods]:Polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) were performed to detected the genotypes of 417 cases with chronic hepatitis B,402 asymptomatic carriers(ASC) with chronic HBV infection,453 cases with HCC and 729 cases of normal population with HBsAg negative.We compared the different genotypes and the relationship between the polymorphism and thesusceptibility to the diseases above. Single Factors such as the age,sex and the distribution of different genotypes were analysed by%2 test. The odds ratios and 95% confidence intervals,as well as the p values of different genetypes betweet groups were estimited by logistic regression after adjustment for age and sex.[Results]:The distribution of genetypes of the genetic variants in cases and controls was consistent with Hardy-Weinberg equilibrium. We observed that rs3077-A can significantly reduce the risk of chronic hepatitis B, acting in an allele dose-dependent manner. Further analysis demonstrated that the allele also reduced the risk of the ASC, HBsAg positive HCC as well as the overall HCC, and also showed the allele-dose relationship. However, the allele was not correlated with the risk of HCC with HBsAg negative, and not correlated with the risk of progression from HBV carriers to HCC either., but had an effect to promote the progression form chronic hepatitis B to HCC.[Conclusions]:Based on these results above we conclude that rs3077 is also associated with genetic susceptibility to chronic hepatitis B in Chinese population. In addition, this genetic variant may play an improtant role in the different outcomes of the HBV infection, as well as the development of HCC. Make clear the different genotypes in different individuals may provide us important clues for individualized prevention and treatment strategies.