Association between HLA-DQ Gene rs2856178A>G, rs9275572A>G Polymorphisms and the Risk of Chronic Hepatitis B: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 XIANGxin ^1,2 , YANGLi ² , GUOYu-xuan ² ,  XUFei-li ²

1. College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830000, China;
2. Clinical Laboratory Center of TCM Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, China;

Corresponding author：

XUFei-li, Email: xfl6284@163.com

Keywords：

Human leukocyte antigen DQ gene; Polymorphism; Hepatitis B; chronic; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20150189

Video：

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Objective To systematically evaluate the association between human leukocyte antigen DQ (HLA-DQ) gene rs2856718A>G, rs9275572A>G polymorphisms and the risk of chronic hepatitis B. Methods PubMed, EMbase, CBM, WanFang Data, CNKI and VIP databases were systematically searched from inception to April 2015 to collect case-control studies about HLA-DQ gene polymorphisms and the risk of chronic hepatitis B. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software, and Stata 12.0 software was used for sensitivity and publication bias analysis. Results A total of 6 papers involving 8 case-control studies were included, which involved 3 690 cases and 6 267 controls. The results of meta-analysis showed that:the rs2856718A>G polymorphism was associated with the decreased risk of chronic hepatitis B (AG+GG vs. AA:OR=0.63, 95%CI 0.51 to 0.78, P=0.000; GG vs. AG+AA:OR=0.69, 95%CI 0.61 to 0.79, P=0.000; GG vs. AA:OR=0.56, 95%CI 0.48 to 0.64, P=0.000; GA vs. AA:OR=0.64, 95%CI 0.47 to 0.88, P=0.006; G vs. A:OR=0.74, 95%CI 0.68 to 0.79, P=0.000). The rs9275572A>G polymorphism was not associated with the risk of chronic hepatitis B (AG+GG vs. AA:OR=1.11, 95%CI 0.55 to 2.23, P=0.770; GG vs. AG+AA:OR=1.10, 95%CI 0.84 to 1.45, P=0.500; GG vs. AA:OR=1.14, 95%CI 0.54 to 2.41, P=0.730; AG vs. AA:OR=1.06, 95%CI 0.56 to 2.02, P=0.860; G vs. A:OR=1.11, 95%CI 0.83 to 1.48, P=0.490). Conclusion HLA-DQ gene rs2856718 A>G polymorphism is significantly associated with decreased risk of chronic hepatitis B, but the rs9271319 A>G polymorphism is not associated with the risk of chronic hepatitis B.

Citation： XIANGxin, YANGLi, GUOYu-xuan, XUFei-li. Association between HLA-DQ Gene rs2856178A>G, rs9275572A>G Polymorphisms and the Risk of Chronic Hepatitis B: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(10): 1137-1141. doi: 10.7507/1672-2531.20150189 Copy

1.	福军亮, 徐东平, 赵平, 等. 急慢性乙型肝炎患者外周血调节性T细胞鉴定与临床意义分析. 中华医学杂志, 2006, 86(22):1522-1525.
2.	Du YP, Deng CS, Lu DY, et al. The relation between HLA-DQAl genes and genetic susceptibility to duodenal ulcer in Wuhan Hans. World J Gastroenterol, 2000, 6(1):107-110.
3.	Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol, 2001, 19(1):65-91.
4.	Abel L, Dessein AJ. The impact of host genetics on susceptibility to human infectious diseases. Curr Opin Immunol, 1997, 9(4):509-516.
5.	McNicholl JM, Cuenco KT. Host genes and infectious diseases. HIV, other pathogens, and a public health perspective. Am J Prev Med, 1999, 16(2):141-154.
6.	Thursz M. Genetic susceptibility in chronic viral hepatitis. Antiviral Res, 2001, 52(6):113-116.
7.	Jung MC, Pape GR. Immunology of hepatitis B infection. Lancet Infect Dis, 2002, 2(1):43-50.
8.	Gheuens S, Fellay J, Goldstein DB, et al. Role of human leukocyte antigen class I alleles in progressive muhifocal leukoencephalopathy. J Neurovirol, 2010, 16(1):41-47.
9.	中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2010年版). 中华传染病学杂志, 2011, 29(2):65-80.
10.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9):603-605.
11.	Al-Qahtani A, Al-Anazi M, Abdo A, et al. Association between HLA variations and chronic hepatitis B virus infection in Saudi Arabian patients. PLoS ONE, 2014, 9(1):e80445.
12.	Zhang X, Jia J, Dong J, et al. HLA-DQ polymorphisms with HBV infection:different outcomes upon infection and prognosis to lamivudine therapy. J Viral Hepatitis, 2014, 21(7):491-498.
13.	Mbarek H, Ochi H, Urabe Y, et al. A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Hum Mol Genet, 2011, 20(9):3884-3892.
14.	Hu L, Zhai X, Liu J, et al. Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development. Hepatology, 2012, 55(5):1426-1431.
15.	Hou SH, Hu J, Zhang Y, et al. Effects of interaction between genetic variants in human leukocyte antigen DQ and granulysin genes in Chinese Han subjects infected with hepatitis B virus. Microbiol Immunol, 2015, 59(4):209-218.
16.	Chen K, Shi W, Xin Z. Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci in a Chinese population. PLoS One, 2013, 8(10):e77315.
17.	Jiang YG, Wang YM, Liu TH, et al. Association between HLAⅡ gene and susceptibility or resistance to chronic hepatitis B. World J Gastroenterol, 2003, 9(10):2221-2225.
18.	Park MH, Song EY, Ahn C, et al. Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans. Tissue Antigens, 2003, 62(6):505-511.
19.	Guo X, Zhang Y, Li J, et al. Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population. Hepatology, 2011, 53(2):422-428.
20.	Wang L, Wu XP, Zhang W, et al. Evaluation of genetic susceptibility loci for chronic hepatitis B in Chinese:two independent case-control studies. PLoS One, 2011, 6 (3):e17608.
21.	Lau KC, Lam CW, Law CY, et al. Non-invasive screening of HLA-DPA1 and HLA-DPB1 alleles for persistent hepatitis B virus infection:susceptibility for vertical transmission and toward a personalized approach for vaccination and treatment. Clin Chim Acta, 2011, 412(11-12):952-957.
22.	Vermehren J, Lotsch J, Susser S, et al. A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers. PLoS One, 2012, 7(3):e32605.
23.	Nishida N, Sawai H, Matsuura K, et al. Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. PLoS One, 2012, 7(6):e39175.
24.	Wong DK, Watanabe T, Tanaka Y, et al. Role of HLA-DP polymorphisms on chronicity and disease activity of hepatitis B infection in Southern Chinese. PLoS One, 2013, 8(6):e66920.
25.	Ferrari C, Penna A, Bertoletti A, et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. Immunol, 1990, 145(10):3442-3449.
26.	Milich DR. T-and B-cell recognition of hepatitis B viral antigens. Immunol Today, 1988, 9(12):380-386.
27.	Nayersina R, Fowler P, Guilhot S, et al. HLA-A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. J Immunol, 1993, 150(10):4659-4671.

1. 福军亮, 徐东平, 赵平, 等. 急慢性乙型肝炎患者外周血调节性T细胞鉴定与临床意义分析. 中华医学杂志, 2006, 86(22):1522-1525.
2. Du YP, Deng CS, Lu DY, et al. The relation between HLA-DQAl genes and genetic susceptibility to duodenal ulcer in Wuhan Hans. World J Gastroenterol, 2000, 6(1):107-110.
3. Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol, 2001, 19(1):65-91.
4. Abel L, Dessein AJ. The impact of host genetics on susceptibility to human infectious diseases. Curr Opin Immunol, 1997, 9(4):509-516.
5. McNicholl JM, Cuenco KT. Host genes and infectious diseases. HIV, other pathogens, and a public health perspective. Am J Prev Med, 1999, 16(2):141-154.
6. Thursz M. Genetic susceptibility in chronic viral hepatitis. Antiviral Res, 2001, 52(6):113-116.
7. Jung MC, Pape GR. Immunology of hepatitis B infection. Lancet Infect Dis, 2002, 2(1):43-50.
8. Gheuens S, Fellay J, Goldstein DB, et al. Role of human leukocyte antigen class I alleles in progressive muhifocal leukoencephalopathy. J Neurovirol, 2010, 16(1):41-47.
9. 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2010年版). 中华传染病学杂志, 2011, 29(2):65-80.
10. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9):603-605.
11. Al-Qahtani A, Al-Anazi M, Abdo A, et al. Association between HLA variations and chronic hepatitis B virus infection in Saudi Arabian patients. PLoS ONE, 2014, 9(1):e80445.
12. Zhang X, Jia J, Dong J, et al. HLA-DQ polymorphisms with HBV infection:different outcomes upon infection and prognosis to lamivudine therapy. J Viral Hepatitis, 2014, 21(7):491-498.
13. Mbarek H, Ochi H, Urabe Y, et al. A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Hum Mol Genet, 2011, 20(9):3884-3892.
14. Hu L, Zhai X, Liu J, et al. Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development. Hepatology, 2012, 55(5):1426-1431.
15. Hou SH, Hu J, Zhang Y, et al. Effects of interaction between genetic variants in human leukocyte antigen DQ and granulysin genes in Chinese Han subjects infected with hepatitis B virus. Microbiol Immunol, 2015, 59(4):209-218.
16. Chen K, Shi W, Xin Z. Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci in a Chinese population. PLoS One, 2013, 8(10):e77315.
17. Jiang YG, Wang YM, Liu TH, et al. Association between HLAⅡ gene and susceptibility or resistance to chronic hepatitis B. World J Gastroenterol, 2003, 9(10):2221-2225.
18. Park MH, Song EY, Ahn C, et al. Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans. Tissue Antigens, 2003, 62(6):505-511.
19. Guo X, Zhang Y, Li J, et al. Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population. Hepatology, 2011, 53(2):422-428.
20. Wang L, Wu XP, Zhang W, et al. Evaluation of genetic susceptibility loci for chronic hepatitis B in Chinese:two independent case-control studies. PLoS One, 2011, 6 (3):e17608.
21. Lau KC, Lam CW, Law CY, et al. Non-invasive screening of HLA-DPA1 and HLA-DPB1 alleles for persistent hepatitis B virus infection:susceptibility for vertical transmission and toward a personalized approach for vaccination and treatment. Clin Chim Acta, 2011, 412(11-12):952-957.
22. Vermehren J, Lotsch J, Susser S, et al. A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers. PLoS One, 2012, 7(3):e32605.
23. Nishida N, Sawai H, Matsuura K, et al. Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. PLoS One, 2012, 7(6):e39175.
24. Wong DK, Watanabe T, Tanaka Y, et al. Role of HLA-DP polymorphisms on chronicity and disease activity of hepatitis B infection in Southern Chinese. PLoS One, 2013, 8(6):e66920.
25. Ferrari C, Penna A, Bertoletti A, et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. Immunol, 1990, 145(10):3442-3449.
26. Milich DR. T-and B-cell recognition of hepatitis B viral antigens. Immunol Today, 1988, 9(12):380-386.
27. Nayersina R, Fowler P, Guilhot S, et al. HLA-A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. J Immunol, 1993, 150(10):4659-4671.

Chinese Journal of Evidence-Based Medicine

Association between HLA-DQ Gene rs2856178A>G, rs9275572A>G Polymorphisms and the Risk of Chronic Hepatitis B: A Meta-analysis

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