Correlation between polymorphisms in the human leukocyte antigen-DQB1 alleles and hepatitis B with primary hepatocellular carcinoma

Abstract

To investigate the correlation between polymorphisms in human leukocyte antigen (HLA)-DQB 1 and primary liver cancer (PLC) with hepatitis B virus (HBV) and to search for susceptibility and resistance genes related to PLC with HBV. One hundred and eighteen patients with HBV-related liver cancer were enrolled from the First Hospital of Shanxi Medical University. Patients were stratified by family history of hepatitis B (39 with; 79 without) and HBV DNA positivity (60 positive, ≥1*10(3) IU/mL; 58 negative, <1*10(3) IU/mL). The HLA-DQB 1 genotype was determined by PCR and direct nucleotide sequence analysis genotyping. Allele frequencies were calculated by the direct counting method. Betweengroup comparisons were carried out with the Chi-square test or Mann-Whitney U test. The allele frequencies of HLA-DQBl*0202 and HLA-DQBl*0301 were significantly higher in patients with hepatocellular carcinoma (HCC) than the control group (1 1.8% and 29.3% vs. 7.6% and 21.1%; U=2.43 and 3.09, P<0.05, RR=1.581 and 1.477). The allele frequencies of HLA-DQB1*0202 and HLADQB 1*0301 were significantly higher in patients with HCC and familial history of hepatitis B than in the normal population (14.1% and 29.5% vs. 7.6% and 21.1%; U=3.76 and 3.16, P less than 0.05, RR=1.928 and 1.495). The allele frequency of HLA-DQB 1*0301 was significantly higher in the HBV DNA positive group than in the HBV DNA negative group (35.0% vs. 23.3%; x2=5.543, P less than 0.05, RR=1.775), while the frequency of HLA-DQB1*0302 was significantly lower in the HBV DNA positive group than in the HBV DNA negative group (10.9% vs. 14.7%; x2=4.604, P<0.05, RR=0.229). The HLA-DQB 1 *0202 and HLA-DQB 1*0301 alleles may represent susceptibility for PLC with hepatitis B as well as for familial hepatitis B liver cancer. The HLA-DQB 1*0301 allele may support replication of HBV DNA, facilitating progression to liver cancer. The HLA-DQB1*0302 allele may inhibit replication of HBV DNA and reduce the incidence of liver cancer.