Roles Of Non-classical MHC-I Genes In Chronic Hepatitis B And Hepatocellular Carcinoma

Background:The non-classical MHC-I molecules including HLA-E, HLA-G, and HLA-F are modulators of immune responses. Gene polymorphisms and protein expression abnormalities are closely related to kinds of diseases.Purpose:This study aimed to find out whether non-classical HLA polymorphisms are associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in Chinese Han population.Methods:Subjects were categorized into three groups,(1) HBV infection without HCC (n=81; male/female=67/14; mean age=41.3±11.3years),(2) HBV infection with HCC (n=39; male/female=37/2; mean age=51.7±9.5years), and (3) complicated hepatitis B group (n=31; male/female=23/8; mean age=46.1±11.5years). Another267healthy Chinese Han population were included as controls. Fifteen SNPs pertaining to these three genes were investigated by ligase detection reaction (LDR). A length of650bp segment of3’-untranslated region (UTR) of HLA-G was resequenced. Raw data were analyzed by Novosnp, GenAlEX and GENEPOP softwares. Results:Our findings include:(1) updating the frequency data for24SNPs located in non-classical HLA class I molecules in healthy Chinese Han population and HBV/HCC patient,(2) four SNPs (rs17875380, rs41557518, rs114465251, and rs115492845) located in HLA-E,-G, and-F were associated with susceptibility to HBV or HCC,(3) finding out the linkage disequilibrium (LD) patterns of24SNPs,(4) providing frequency data for common HLA-E,-G, and-F alleles in healthy Chinese Han population,(5) elucidating the genetic structure of3’UTR of HLA-G gene,(6) six haplotypes (H4, H8, H11, H14, H15, and H16) concerning HLA-E,-G, and-F genes were associated with susceptibility to HBV or HCC.Conclusion:This study providing credible data as a healthy reference and detailed analyses of non-classical HLA class I polymorphisms can give more genetics and immunologic insights into the mechanism of HBV and HCC.