Associations Of Rs9272346 Polymorphism In HLA-DQA1 Gene And Rs7271350 Polymorphism In SNX5 Gene With Diverse Clinical Outcomes Of Chronic HBV Infection

ObjectiveHepatitis B virus(HBV) infection is a complicated disease caused by virus, multigenes and enviroment factor. It's an useful strategy to determine potential candidate genes of HBV infection for the prevention and individualized treatment. The purpose of this study is to evaluate the distribution differences of rs9272346 polymorphism in HLA-DQA1 and rs7271350 polymorphism in SNX5 gene in Han population of Hubei province, to explore the association of rs9272346 polymorphism in HLA-DQA1 and rs7271350 polymorphism in SNX5 gene with the different outcomes of chronic hepatitis B virus infection in Hubei Han people.MethodsA case-control study was conducted, 798 unrelated chronic HBV infection subjects with progressed outcomes and 236 unrelated chronic asymptomatic HBV carriers as controls were recruited in Han population of Hubei province from Wuhan Tongji Hospital. The 798 patients in the case group were divided into the acute-on-chronic liver failure(ACLF) group, HBV-related liver cirrhosis(LC) group and HBV-related hepatocellular carcinoma(HCC) group.We obtained the blood samples, and collected the materials of medical history and laboratory test results.Using the genome DNA as templates, the genotypes of rs9272346 and rs7271350 were determinated by real-time polymerase chain reaction with the Taqman MGB probe. The statistical data was analyzed by student's t test ,chi square test and unconditional logistic regression.ResultsClinical data shows that the proportion of men and HBeAg positive patients in each case group is higher than that in the control group( p < 0.01 ). For rs9272346 in HLA-DQA1 gene, no statistical differences in the distribution of allele between ACLF,LC,HCC and ASC group was found(p = 0.312, 0.308, 0.264 );After adjusted for age and sex, there were also no significant differences between the case and control group.when the genotype GG plus GA versus genotype AA. We stratified the case-control study by sex factor and found that the the genotype GG plus GA was a protective factor for progression to acute-on-chronic liver failure compared to genotype AA in female patients(OR=0.3,95%CI:0.10~0.87) .As for the rs7271350 polymorphism in SNX5 gene, a statistically significant association with susceptibility to acute hepatic failure was observed with the C allele(P=0.035). Subjects bearing at least one C allele(genotype CC plus CT) had an increased susceptibility to acute hepatic failure compared to those bearing TT genotype(OR=1.876;95%CI:1.064~3.307,P=0.030)with adjustment for age and sex. However no significant associations were found between the genotype and the occurring of liver cirrhosis or hepatocellular carcinoma.ConclusionMale, HBeAg positive chronic HBV infected patients are more susceptible to progress to acute liver failure. The single nucleotide polymorphism of rs9272346 locus in HLA-DQA1 gene may have no associations with different outcomes of chronic hepatitis B virus infection. While the genotype GG and GA may be the protective factor for progression to acute-on-chronic liver failurein female patients. The subjects bearing at least one C allele of rs7271350 in SNX5 gene may have higher risk for progression to acute-on-chronic liver failurecompared to TT genotype.