Association of HLA-DQB1 gene polymorphisms with outcomes of HBV infection in Chinese Han population.

BACKGROUND: Host genetic factors and environmental factors including hepatitis B virus (HBV) genotype are widely studied for the different outcomes of HBV infection. Human leukocyte antigen (HLA) plays an important role in the immunological reaction to HBV infection. AIMS: To explore whether the HLA-DQB1 allele polymorphisms are associated with the outcome of HBV infection in a Chinese Han population. PATIENTS: One hundred and thirty three HBV subjects with spontaneous recovery and 151 chronic hepatitis B patients were recruited into this case-control study in the Beijing area of China. METHODS: Sequence specific primer-polymerase chain reaction (SSP-PCR) was used to detect 13 alleles of HLA-DQB1 gene and 13 alleles of HLA-DRB1 gene. Multivariate logistic regression model was performed to detect the association of candidate factors with outcome of HBV infection by SAS 9.1.2 software package. RESULTS: The frequency of HLA-DQB1*0502 allele in the chronic hepatitis B group was significantly higher than that in the group with spontaneous recovery independent of HLA-DRB1 (odds ratio 95%CI 1.8-190). In this study there was no evidence to indicate that cigarette smoking or alcohol consumption was associated with the outcome of HBV infection. CONCLUSION: HLA-DQB1*0502 is independently associated with the outcome of HBV infection and is one host genetic factor affecting HBV infection outcome. At the same time, we can not rule out the possibility that excluded genes and alleles may also affect outcome.

Association of-238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection.

OBJECTIVES: To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha (TNF-alpha) gene promoter were associated with outcomes of hepatitis B virus infection. METHODS: A total of 246 HBV self-limited infected subjects and 443 chronic hepatitis B (HB) patients were recruited in this case-control study. TNF-alpha-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of TNF-alpha-238 GG (90.7%) in chronic HB group was significantly lower than that (95.1%) in self-limited group (P = 0.041). The frequency of TNF-alpha-857 CC (79.7%) in chronic HB patients was significantly higher than that (70.9%) in self-limited infected subjects (P = 0.021). Multiple logistic regression analysis revealed that both TNF-alpha-238GA and -857CC were independently associated with chronic HB. CONCLUSIONS: TNF-alpha promoter variants are likely to play a substantial role in influencing the outcomes of HBV infection.

[Study on association between vitamin D receptor gene polymorphisms and the outcomes of HBV infection].

OBJECTIVE: To explore whether the vitamin D receptor gene (VDR) polymorphisms are associated with the outcomes of hepatitis B virus (HBV) infection in Chinese Han population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphisms of Fok I locus in exon 2 and Taq I locus in exon 9 of VDR gene. One hundred and eighty-four chronic hepatitis B patients and 205 asymptomatic HBV carriers were recruited to make the comparison of frequencies of genotype and haplotype of the VDR gene between the patients and the carriers. RESULTS: The univariate analysis showed a significant difference in Fok I polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group. The FF genotype frequency in chronic hepatitis B patients group was 44.6%,higher than 31.7% in asymptomatic HBV carriers group (P<0.05). After adjusting the confounders by multiple logistic regression analysis, the result still showed a significant difference in Fok I site polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group (OR=1.95, P<0.05). The FT haplotype frequency in chronic hepatitis B patients group was higher than that in asymptomatic HBV carriers group (OR=1.45, P<0.05). The fT haplotype frequency in chronic hepatitis B patients group was lower than that in asymptomatic HBV carriers group (OR=0.72, P<0.05). CONCLUSION: VDR gene polymorphism may be an influence factor of genetic susceptibility to HBV infection.

[Association of Taq I T/C and Fok I C/T polymorphisms of vitamin D receptor gene with outcome of hepatitis B virus infection].

OBJECTIVE: To determine whether Taq I T/C and Fok I C/T polymorphisms of vitamin D Receptor (VDR) gene was associated with the outcomes of hepatitis B virus (HBV) infection. METHODS: A total of 212 HBV self-limited infection individuals, 244 asymptomatic HBsAg carriers and 391 chronic hepatitis B (HB) patients were recruited to conduct a case-control study. VDR-Taq I T/C and VDR-Fok I C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of VDR-Fok I allele C in the chronic HB patients was 45.8%, significantly higher than 38.2% of the self-limited infection individuals (chi(2) = 6.43, P = 0.01). The frequencies of VDR-Fok I genotypes TT, TC, and CC in HB patients were 30.7%, 47.1%, and 22.2% respectively, and 41.0% (TT), 41.5% (TC), and 17.5% (CC) in the self-limited infection individuals. There was a statistically significant difference between HB patients and self-limited infection individuals (chi(2) = 6.76, P = 0.03). The results of univariate analysis showed that the subjects carrying VDR-Fok I CC/TC genotype had 1.57-fold elevated risk for developing chronic HB when they were infected HBV (OR = 1.57, P = 0.01). A multiple logistic regression analysis revealed that VDR-Fok I CC/CT was independently associated with chronic HB after adjusting both potential confounding effects of gender (OR = 1.70, P = 0.021). The statistically significant association between TaqI T/C polymorphism and outcome of HBV infection was not demonstrated in the study. The frequency of haplotype TC of VDR-TaqI and Fok I in HB patients was 2.3080%, significantly higher than 0.5391% of the self-limited infection individuals (chi(2) = 6.08, P = 0.01). However, the frequency of haplotype TT in the HB patients was 1.5283%, significantly lower than 3.7061% of the self-limited infection individuals (chi(2) = 5.65, P = 0.02) and 3.4820% of the HBV carriers (chi(2) = 5.12, P = 0.02). CONCLUSION: VDR gene polymorphism is probably an influence factor on the genetic susceptibility of HBV infection.

[Relationship between polymorphisms of vitamin D receptor gene and familial aggregation of HBsAg carriers].

OBJECTIVE: To determine whether -Taq I T/C and -Fok I C/T polymorphisms of vitamin D receptor (VDR) gene are associated with the familial aggregation of hepatitis B virus (HBV) infection. METHODS: Based on a population-based case-control family design, 288 family members from 27 case families and 230 family members from 27 control families were recruited. VDR gene polymorphisms were analyzed. VDR-Taq I T/C and VDR-Fok I C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of VDR-Taq I TT genotype in the case families was significantly higher than that in the control families (P < 0.05) , however, the frequency of VDR-Fok I CC genotype in the case families was significantly higher than that in the control families (P < 0.05). The frequency of family members carriying Taq I T-Fok I C haplotype in the case families was significantly higher than that in the control families (OR = 1.67, P < 0.05), however, the frequency of family members carrying Taq I C-Fok I T haplotype in the case families was significantly lower than that in the control families (OR = 0. 24, P < 0.05). The similar results were found in the familial biological kinship relatives with any HBV-infected makers. CONCLUSION: VDR-Taq I and -Fok I gene polymorphisms are likely to play a substantial role in HBsAg familial aggregation.

Association of polymorphism of tumor necrosis factor-alpha gene promoter region with outcome of hepatitis B virus infection.

AIM: To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha (TNF-alpha), gene promoter and hepatitis B (HB) viral genotypes were associated with outcomes of HBV infection. METHODS: A total of 244 HBV self-limited infected subjects, 208 asymptomatic carriers, and 443 chronic HB patients were recruited to conduct a case-control study. TNF-alpha-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and HBV genotypes were examined by nested PCR. RESULTS: The positive rate of HBV DNA in asymptomatic carrier group and chronic HB group was 46.6% and 49.9%, respectively. HBV genotype proportion among the asymptomatic carriers was 2.1% for genotype A, 25.8% for genotype B, 68.0% for genotype C, and 4.1% for genotype B+C mixed infection, and 0.9% for genotype A, 21.7% for genotype B, 71.5% for genotype C, 5.9% for genotype B+C mixed infection in chronic HB group. There was no significant difference in genotype distribution between the asymptomatic carrier group and chronic HB group (chi2 = 1.66, P = 0.647). The frequency of -238GG genotype in self-limited group was 95.1%, significantly higher than 90.7% in chronic HB group and 89.0% in asymptomatic carrier group (P = 0.041 and P = 0.016, respectively). The frequency of TNF-alpha-857 CC in chronic HB group was 79.7%, significantly higher than 64.4% in asymptomatic carrier group and 70.9% in self-limited group (P<0.001 and P = 0.023, respectively). A multiple logistic regression analysis revealed that TNF-alpha-238GA and -857CC were independently associated with chronic HB after gender and age were adjusted. CONCLUSION: TNF-alpha promoter variants are likely to play a substantial role in the outcome of HBV infection.

[Association of TNFA polymorphisms with the outcomes of HBV infection].

OBJECTIVE: To explore whether the TNFA promoter single nucleotide polymorphisms (SNPs) are associated with the outcomes of hepatitis B virus(HBV) infection in Chinese Han population. METHODS: One hundred and forty-eight self-limited HBV infection subjects and 207 chronic hepatitis B patients were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific primer-PCR(PCR-SSP) were used to detect the SNPs of five sites in TNFA promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in different groups were analyzed by EPI and EH programs. RESULTS: The frequencies of -238GG genotype in chronic hepatitis B patients were significantly higher than that in self-limited infection subjects (P=0.02). The frequencies of -857TT genotype in chronic hepatitis B patients were clearly lower than that in self-limited infection subjects (P=0.02). Haplotypic frequencies of GGCCT (-238/-308/-857/-863/-1031) in chronic hepatitis B patients was significantly lower than that in self-limited infection subjects (P=0.03), and the frequencies of haplotype GGCAT or GGTAT in chronic hepatitis B patients were clearly higher than those in self-limited infection subjects (P=0.0001; P=0.004). CONCLUSION: TNFA promoter polymorphisms are important host genetic factors affecting the outcomes of HBV infection.