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

J Transl Med. 2018 Dec 18;16(1):362. doi: 10.1186/s12967-018-1716-z.


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).

Keywords: HBV susceptibility; HLA-DQB1; Spontaneous clearance; mRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cytokines / blood
  • Genetic Predisposition to Disease
  • HLA-DQ beta-Chains / genetics*
  • HLA-DQ beta-Chains / metabolism
  • Hepatitis B / genetics
  • Hepatitis B / virology*
  • Hepatitis B virus / physiology*
  • Meta-Analysis as Topic
  • Polymorphism, Genetic*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Cytokines
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • RNA, Messenger