Association Of HLA-DRB1,-DQA1Polymorphism With The Outcomes Of Hepatitis B Virus Infection In Uygur Population Of Xinjiang

[Background] The body anti-viral immune function and virus to evade immune attackresponse capabilities determine the occurrence, development and outcome of HBV.From occult infection, acute hepatitis and chronic hepatitis and even the development ofcirrhosis and liver cancer are the formation of a complex spectrum of disease. It causedthe disease associated with hepatitis B virus virulence,the genetic background of thehost immune hepatitis B virus infection of immune response is different is moreimportantly. While human leukocyte antigen is the most important genetic factors indetermining human immune response, especially the immune cells of HLA pass thebiological characteristics of the antigenic peptides to antigen-specific T cell receptor.HLA antigen molecule is associated with resistance to HBV immune responses inidentifying, immune response and immune regulation, destroying foreign antigen targetcells, they may affect the strength of the chronic HBV infection and the immuneresponse. Hepatitis B virus infection of immune response depends on the geneticpolymorphism of HLA-Class II, More and more studies have shown that HLA-II genesand HBV susceptibility or resistance correlation determines the prognosis of hepatitis Bvirus infection. Therefore, the HLA-II gene locus is related to infection with thehepatitis B virus gene, current research focus is mainly concentrated in the DR and DQsub-region.Chronic hepatitis B virus infection is one of the common infection disease in China,The incidence of hepatitis B have significant regional and ethnic differences,Existing chronic hepatitis B virus infection of about9300million and including about20million cases of patients with chronic hepatitis B.HLA polymorphisms and hepatitisB virus infection research in recent years become the hot spots of the liver diseasecommunity at home and abroad.Commenced in different parts of the crowd began tostudy and have made some progress, but the results there are obvious regional andethnic differences.Human leukocyte antigen allele frequencies between the differentraces is a significant difference. Therefore, the HLA gene frequency distribution inUygur population of Xinjiang is meaningful, Finding genetic susceptibility genes andresistance genes to the Xinjiang Uygur HBV infection is of great significance on theclinical judgment of HBV infection outcome and prognosis and to carry out individualtreatment and prevention.[Objective]To explore human leukocyte antigen (HLA)-DRB1,-DQA1allele frequencies inthe different outcomes of hepatitis B virus infection, To investigate the associations ofHLA-DRB1,-DQA1polymorphism with the outcome of hepatitis B virus infection andthe replication of HBV in Uygur population of Xinjiang.[Methods]This study adopted candidate genes strategy and case-control design.The subjectswere divided into four groups in Uygur population of Xinjiang from Apr.2010to Mar.2011：70chronic hepatitis B patients(CHB group)，46chronic asymptomatic hepatitis Bvirus carriers (Carriers group)，42spontaneous rehabilitee after HBV infection(Rehabilitee group) and80healthy controls were recruited. Genomic DNA wasextracted from peripheral blood smaples.1) The HBV relative antigens and antibodies systems (including HBsAg、anti-HBs、HBeAg、anti-HBe、anti-HBc) were detected by ELISA;2) The quantity of HBV DNA was measured by PCR fluorescent probing, the frequency distributions of genotype among four groups were analyzed;3) HLA-DRBl,-DQA1alleles were detected by the polymerase chainreaction/sequence specific primer (PCR/SSP) technique. the frequency of thatin different replication of HBV was studied;4) The positive results of HLA-DRB1,-DQA1allele was amplified by PCR werepurified and sequenced, the results of the homology argument analysis byBLAST gene service station.[Results]1) The frequency of HLA-DRB1*0701allele in spontaneous rehabilitee group(13.09％) and healthy controls group (13.75％) were significantly higher thanthose in chronic hepatitis B patients (5.71％)(χ~2=4.06、6.03,P<0.05，OR=0.36、0.34), and in chronic asymptomatic HBV carriers group (4.35﹪)(χ~2=4.75、6.31，P<0.05；OR=0.27、0.25)；The frequency of HLA-DRB1*1201-3allelein spontaneous rehabilitee group was higher than those in chronic hepatitis Bpatients (16.67％：7.86％，χ~2=4.70、P<0.05，OR=0.37)；The frequencies ofHLA-DRB1*1301-2in healthy controls group and spontaneous rehabiliteegroup were9.38％and10.70％，significantly higher than those in chronichepatitis B patients (χ~2=14.58、13.54，P<0.01);2) The frequency of HLA-DQA1*0102allele in spontaneous rehabilitee group(23.81％) and healthy controls group (22.50％) were significantly higher thanthose in chronic hepatitis B patients (10.00％)(χ~2=9.47、10.50， P<0.01，OR=0.28、0.31), and in chronic asymptomatic HBV carriers (8.69％)(χ~2=9.25、9.79，P<0.01，OR=0.23、0.26)；The frequency of HLA-DQA1*0501in chronicasymptomatic HBV carriers was higher than those in healthy controls group(21.39％：13.13％，χ~2=3.95、P<0.05，OR=2.16). In addition, the frequency ofHLA-DQA1*0501in chronic hepatitis B patients (27.14％) was markedlyhigher than those in spontaneous rehabilitee group (15.48％) and healthycontrols group (13.13％)(χ~2=5.76， P<0.01， OR=2.65；χ~2=12.30， P<0.01， OR=3.34);3) The frequencies of other DRB1,DQA1alleles were not significantly differentamong the groups，and the same result was observed in different replication ofHBV(P>0.05).[Conclusion]The subjects with HLA-DQA1*0501allele have an increased risk to chronichepatitis B infection compared with other subjects without this allele, while Alleles ofHLA-DRB1*1201-3,DRB1*1201-3,DRB1*1301-2and HLA-DQA1*0102are closelyassociated with HBV clearance in Uygur population of Xinjiang．...