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The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection.

ABSTRACT: BACKGROUND:Infection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections. METHODS:This study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case-control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance. RESULTS:We found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02. CONCLUSION:DBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).

SUBMITTER: Ou G

PROVIDER: S-EPMC6299522 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection.

Ou Guojin G Xu Haixia H Yu Hao H Liu Xiao X Yang Liu L Ji Xin X Wang Jue J Liu Zhong Z

Journal of translational medicine 20181218 1

<h4>Background</h4>Infection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections.<h4>Methods</h4>This study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interle ...[more]

PMID: 30563535

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Project description:Single-nucleotide polymorphisms in the human leukocyte antigen (HLA)-DQB1 gene are associated with chronic inflammatory and immunological diseases. Host genetic factors have a key role in the development of chronic hepatitis B (CHB). The aim of the present study was to investigate the association between the HLA-DQB1 polymorphisms and the susceptibility to CHB. PubMed, Embase, CNKI and Wanfang databases were searched for the studies that reported the association of the HLA-DQB1 polymorphisms with CHB between January 1, 1966 and July 30, 2015. HLA-DQB1 polymorphism-specific odds ratio (OR) and 95% confidence intervals (95% CI) were pooled and calculated in the fixed effects model using the Mantel-Haenszel method. Q-test and I2 test were performed to examine the heterogeneity. Begg's funnel test and Egger's test were conducted to assess publication bias. All the statistical tests were two-tailed. Subsequent to searching the databases and screening according to the inclusion criteria, 7 case-control studies were available in the present meta-analysis, including 815 CHB patients and 731 control subjects for the HLA-DQB1 polymorphisms. In conclusion, the statistically significant pooled OR of the HLA-DQB1 polymorphisms were obtained for the HLA-DQB1 loci (*0201, case vs.ControlI2=36.5%; P-value of heterogeneity=0.15; OR, 1.29; 95% CI, 1.02-1.64; P=0.0301; *0301, case vs.ControlI2=0%; P-value of heterogeneity=0.899; OR, 1.37; 95% CI, 1.12-1.69; P=0.002; *0502, case vs.ControlI2=24.9%; P-value of heterogeneity=0.239; OR, 1.50; 95% CI, 1.02-2.20; P=0.04), which were associated with an increased risk of CHB. Similar significant results were observed and acquired in the following HLA-DQB1 loci (*0303, case vs.ControlI2=0%; P-value of heterogeneity=0.986; OR, 0.77; 95% CI, 0.62-0.95; P=0.017; *0604, case vs.ControlI2=0%; P-value of heterogeneity=0.594; OR, 0.38; 95% CI, 0.20-0.74; P=0.003), which were associated with a decreased risk of CHB. No significant association was observed for the other HLA-DQB1 family loci. The present meta-analysis demonstrated that the HLA-DQB1 loci (*0201, *0301 and *0502) polymorphisms were significantly associated with an increased risk of CHB. However, HLA-DQB1 loci polymorphisms (*0303 and *0604) were associated with a decreased risk of CHB. These results support the hypothesis that polymorphisms of the HLA-DQB1 allele families may affect the susceptibility or resistance to CHB.

Project description:Potential correlation of human papillomavirus (HPV) 16 E6 variants and human leukocyte antigen (HLA) class II polymorphisms has been suggested in patients with cervical cancer, so far little information is available about the possible interaction between E6 variants and HLA class II variability during the obviously accelerated progression to cervical cancer in young women. In this study, we aimed to explore the association between the HPV16 E6 variants and HLA-DRB1, DQB1 alleles in a Chinese young cervical cancer population. The HLA-DRB1, HLA-DQB1 polymophisms were genotyped by low-resolution polymerase chain reaction (PCR) with sequence-specific primer. HPV16 E6 DNA was tested by Sanger fluorescent dye dideoxy-termination technique. The difference of DRB1, DQB1 polymorphisms between young cervical cancer patients (≤35ys, n=61) and older ones (>35ys, n=85) and the association with E6 variants were analyzed. Results showed that the distribution pattern of HLA-DRB1, DQB1 alleles was different between young cervical cancer patients and older ones. The allele frequency of DQB1*0501 in young patients was significantly lower than older ones (6.6% vs. 23.5%, p<0.05). The HPV16 E6 A4 lineage was the exclusive type observed in young patients, and its prevalence was significantly higher than that of older cases (82.86% vs.41.94%, p<0.05). DRB1*03 was not found in young patients positive for the HPV16 E6 A4 lineage, whereas it was observed in 19.2 % older patients with A4 positive(Pc<0.05). In conclusion, specific association between certain HPV16 E6 variant and genetic polymorphisms of HLA may play a role during the progression of early onset cervical cancer in young patients. Certain HLA-DRB1 and HLA-DQB1 alleles may be related to the A4 lineage among young cervical cancer patients, which was the unique HPV16 E6 variant found in Chinese young patients. Our finding may provide an insight into the pathogenic factors that associated with cervical cancer in young women.

Dataset Information

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection.

Publications

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection.

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