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. 2017 Dec 5;9(1):96-109.
doi: 10.18632/oncotarget.22941. eCollection 2018 Jan 2.

Quantitative assessment of HLA-DQ gene polymorphisms with the development of hepatitis B virus infection, clearance, liver cirrhosis, and hepatocellular carcinoma

Tao Xu  1   2 , Anyou Zhu  3 , Meiqun Sun  4 , Jingzhu Lv  5 , Zhongqing Qian  6   7 , Xiaojing Wang  8 , Ting Wang  6   7   9 , Hongtao Wang  6   7
Affiliations

Quantitative assessment of HLA-DQ gene polymorphisms with the development of hepatitis B virus infection, clearance, liver cirrhosis, and hepatocellular carcinoma

Tao Xu et al. Oncotarget. .

Abstract

Hepatitis B is one of the most common infectious diseases, which leads to public health problems in the world, especially in Asian counties. In recent years, extensive human genetic association studies have been carried out to identify susceptible genes and genetic polymorphisms to understand the genetic contributions to the disease progression of HBV infection. HLA-DQ gene variations have been reported to be associated with HBV infection/clearance, disease progression and the development of hepatitis B-related complications, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC). However, the results are either inconclusive or controversial. Therefore, to derive a more precise estimation of the association, a meta-analysis was performed. Our data revealed that the HLA-DQ alleles rs2856718-G, rs7453920-A and rs9275319-G were significantly associated with decreased risk of HBV infection and HBV natural clearance. Logistic regression analyses showed that HLA-DQ alleles rs9275572-A significantly increased HBV infection clearance, and decreased HBV natural clearance. However, rs2856718-G and rs9275572-A were not associated with development of cirrhosis. The HLA-DQ polymorphisms (rs2856718 and rs9275572) were associated with a decreased HBV-related HCC risk in all genetic models, but rs9272105-A increased the risk of HBV-related HCC. In addition, no significant association was observed between HLA-DQ rs9275319-G polymorphism and HBV-related HCC. These stratified analyses were limited due to relatively modest size of correlational studies. In future, further investigation on a large population and different ethnicities are warranted. Our findings contribute to the personalized care and prognosis in hepatitis B.

Keywords: HLA-DQ; Hepatitis B virus; Immunology; Polymorphism; hepatocellular carcinoma; liver cirrhosis.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. The flow charts of literature search and study selection
Figure 2
Figure 2. Host HLA-DQ region polymorphisms influencing infection outcomes
Figure 3
Figure 3. Forest plots for HLA-DQ rs2856718 polymorphism and HBV infection outcomes
A. HBV infection vs. Control (AA vs. AG+GG); B. HBV infection vs. NC (AA vs. AG+GG); C. LC vs. CHB (AA vs. AG+GG); D. HCC vs. LC+CHB (AA vs. AG+GG).
Figure 4
Figure 4. Forest plots for HLA-DQ rs9275572 polymorphism and HBV infection outcomes
A. HBV infection vs. Control (AA vs. AG+GG); B. HBV infection vs. NC (AA vs. AG+GG); C. LC vs. CHB (AA vs. AG+GG); D. HCC vs. LC+CHB (AA vs. AG+GG)
Figure 5
Figure 5. Forest plots for HLA-DQ rs7453920 polymorphism and HBV infection outcomes
A. HBV infection vs. Control (AA vs. AG+GG); B. HBV infection vs. NC (AA vs. AG+GG).
Figure 6
Figure 6. Forest plots for HLA-DQ rs9275319 polymorphism and HBV infection outcomes
A. HBV infection vs. Control (AA vs. AG+GG); B. HBV infection vs. NC (AA vs. AG+GG); C. HCC vs. LC+CHB (AA vs. AG+GG).
Figure 7
Figure 7. Forest plots for HLA-DQ rs9272105 polymorphism and HBV infection outcomes
HCC vs. LC+CHB (AA vs. AG+GG).
See this image and copyright information in PMC

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