Skip to main content

Advertisement

SpringerLink
Log in

Non-classical MHC-Ι genes in chronic hepatitis B and hepatocellular carcinoma

  • Brief Communication
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The non-classical human leukocyte antigens (HLA)-E, HLA-G, and HLA-F have been shown to modulate immune responses. We examined whether non-classical HLA polymorphisms are associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). Fifteen Single-nucleotide polymorphisms (SNPs) in these non-classical class I alleles were investigated by ligase detection reaction. A fragment of 650 bp located in the 3' untranslated region of HLA-G was investigated. Four SNPs (rs17875380, rs41557518, rs114465251, and rs115492845) were associated with altered susceptibility to HBV or HCC, and HLA-F*01:04, HLA-G*01:05N, and HLA-E*01:01 were associated with hepatitis B or hepatitis B complicated with HCC. Six of 16 designated HLA-E, -G, and -F haplotypes were associated with risk of hepatitis B or HCC. Our study provides healthy reference and detailed analyses of non-classical HLA class Ι polymorphisms that provide insight into immune mechanisms involved in susceptibility to hepatitis B and HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Abbreviations

HLA:

Human leukocyte antigen

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

UTR:

Untranslated region

HCC:

Hepatocellular carcinoma

LDR:

Ligase detection reaction

SNP:

Single-nucleotide polymorphism

LD:

Linkage disequilibrium

MHC:

Major histocompatibility complex

Indel (Ins/Del:

I/D), Insertion/deletion

LOD:

Log odds

GVHD:

Graft versus host disease

References

  • Bigger CB, Guerra B, Brasky KM, Hubbard G, Beard MR, Luxon BA, Lemon SM, Lanford RE (2004) Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees. J Virol 78:13779–13792

    Article  PubMed  CAS  Google Scholar 

  • Cai MY, Xu YF, Qiu SJ, Ju MJ, Gao Q, Li YW, Zhang BH, Zhou J, Fan J (2009) Human leukocyte antigen-G protein expression is an unfavorable prognostic predictor of hepatocellular carcinoma following curative resection. Clin Cancer Res 15:4686–4693

    Article  PubMed  CAS  Google Scholar 

  • Casro MJ, Morales P, Rojo-Amigo R, Martinez-Laso J, Allende L, Varela P, Garcia-Berciano M, Guillen-Perales J, Arnaiz-Villena A (2000) Homozygous HLA-G*0105N healthy individuals indicate that membrane-anchored HLA-G1 molecule is not necessary for survival. Tissue Antigens 56:232–239

    Article  PubMed  CAS  Google Scholar 

  • Castelli EC, Mendes-Junior CT, Deghaide NH, de Albuquerque RS, Muniz YC, Simoes RT, Carosella ED, Moreau P, Donadi EA (2010) The genetic structure of 3' untranslated region of the HLA-G gene: polymorphisms and haplotypes. Gene Immun 11:134–141

    Article  CAS  Google Scholar 

  • Consiglio CR, Veit TD, Monticielo OA, Mucenic T, Xavier RM, Brenol JC, Chies JA (2011) Association of the HLA-G gene +3142C>G polymorphism with systemic lupus erythematosus. Tissue Antigens 77(6):540–545

    Article  PubMed  CAS  Google Scholar 

  • Crispim JC, Duarte RA, Soares CP, Costa R, Silva JS, Mendes-Junior CT, Wastowski IJ, Faggioni LP, Saber LT, Donadi EA (2008) Human leukocyte antigen-G expression after kidney transplantation is associated with a reduced incidence of rejection. Transpl Immunol 18:361–367

    Article  PubMed  CAS  Google Scholar 

  • Danzer M, Polin H, Proll J, Haunschmid R, Hofer K, Stabentheiner S, Hackl C, Kasparu H, Konig J, Hauser H, Binder M, Weiss R, Gabriel C, Krieger O (2009) Clinical significance of HLA-E*0103 homozygosity on survival after allogeneic hematopoietic stem-cell transplantation. Transplantation 88:528–532

    Article  PubMed  CAS  Google Scholar 

  • Ferguson R, Ramanakumar AV, Richardson H, Tellier PP, Coutlee F, Franco EL, Roger M (2011) Human leukocyte antigen (HLA)-E and HLA-G polymorphisms in human papillomavirus infection susceptibility and persistence. Hum Immunol 72(4):337–341

    Article  PubMed  CAS  Google Scholar 

  • Guo X, Zhang Y, Li J, Ma J, Wei Z, Tan W, O'Brien SJ (2011) 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 53:422–428

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Burke P, Yang Y, Seiss K, Beamon J, Cung T, Toth I, Pereyra F, Lichterfeld M, Yu XG (2010) Soluble HLA-G inhibits myeloid dendritic cell function in HIV-1 infection by interacting with leukocyte immunoglobulin-like receptor B2. J Virol 84:10784–10791

    Article  PubMed  CAS  Google Scholar 

  • Huang YW, Hu CY, Chen CL, Liao YT, Liu CJ, Lai MY, Chen PJ, Yang SS, Hu JT, Chen DS, Kao JH (2009) Human leukocyte antigen-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus. J Med Virol 81:588–593

    Article  PubMed  Google Scholar 

  • Khalil-Daher I, Riteau B, Menier C, Sedlik C, Paul P, Dausset J, Carosella ED, Rouas-Freiss N (1999) Role of HLA-G versus HLA-E on NK function: HLA-G is able to inhibit NK cytolysis by itself. J Reprod Immunol 43:175–182

    Article  PubMed  CAS  Google Scholar 

  • Kim JJ, Hong SJ, Hong YM, Kim S, Kang MJ, Kim KJ, Seo EJ, Yoo HW, Cheong HS, Shin HD, Park IS, Lee JK (2008) Genetic variants in the HLA-G region are associated with Kawasaki disease. Hum Immunol 69:867–871

    Article  PubMed  CAS  Google Scholar 

  • Lajoie J, Massinga Loembe M, Poudrier J, Guedou F, Pepin J, Labbe AC, Alary M, Roger M (2010) Blood soluble human leukocyte antigen G levels are associated with human immunodeficiency virus type 1 infection in Beninese commercial sex workers. Hum Immunol 71:182–185

    Article  PubMed  CAS  Google Scholar 

  • Lee N, Ishitani A, Geraghty DE (2010) HLA-F is a surface marker on activated lymphocytes. Eur J Immunol 40:2308–2318

    Article  PubMed  CAS  Google Scholar 

  • Lin A, Zhang X, Ruan YY, Wang Q, Zhou WJ, Yan WH (2011) HLA-F expression is a prognostic factor in patients with non-small-cell lung cancer. Lung Cancer (in press)

  • Ludajic K, Rosenmayr A, Fae I, Fischer GF, Balavarca Y, Bickeboller H, Kalhs P, Greinix HT (2009) Association of HLA-E polymorphism with the outcome of hematopoietic stem-cell transplantation with unrelated donors. Transplantation 88:1227–1228

    Article  PubMed  Google Scholar 

  • Matte C, Lacaille J, Zijenah L, Ward B, Roger M (2000) HLA-G and HLA-E polymorphisms in an indigenous African population. The ZVITAMBO Study Group. Hum Immunol 61:1150–1156

    Article  PubMed  CAS  Google Scholar 

  • Nattermann J, Feldmann G, Ahlenstiel G, Langhans B, Sauerbruch T, Spengler U (2006) Surface expression and cytolytic function of natural killer cell receptors is altered in chronic hepatitis C. Gut 55:869–877

    Article  PubMed  CAS  Google Scholar 

  • Noguchi K, Isogai M, Kuwada E, Noguchi A, Goto S, Egawa K (2004) Detection of anti-HLA-F antibodies in sera from cancer patients. Anticancer Res 24:3387–3392

    PubMed  CAS  Google Scholar 

  • Park KS, Park JS, Nam JH, Bang D, Sohn S, Lee ES (2007) HLA-E*0101 and HLA-G*010101 reduce the risk of Behcet’s disease. Tissue Antigens 69:139–144

    Article  PubMed  CAS  Google Scholar 

  • Park M, Kim DJ, Kim KJ, Hong CB, Kim YJ, Cheong HS, Shin HD, Lee EJ, Kim HN, Chung HW, Kim EK, Lee JY, Kim HL (2009) Genetic associations of common deletion polymorphisms in families with Avellino corneal dystrophy. Biochem Biophys Res Commun 387:688–693

    Article  PubMed  CAS  Google Scholar 

  • Petrie EJ, Clements CS, Lin J, Sullivan LC, Johnson D, Huyton T, Heroux A, Hoare HL, Beddoe T, Reid HH, Wilce MC, Brooks AG, Rossjohn J (2008) CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence. J Exp Med 205:725–735

    Article  PubMed  CAS  Google Scholar 

  • Pyo CW, Williams LM, Moore Y, Hyodo H, Li SS, Zhao LP, Sageshima N, Ishitani A, Geraghty DE (2006) HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the nonclassical class I genes. Immunogenetics 58:241–251

    Article  PubMed  CAS  Google Scholar 

  • Rahimi R, Hosseini AZ, Yari F (2010) The polymorphism of human leucocyte antigen-G gene in a healthy population of Iran. Int J Immunogenet 37:269–272

    Article  PubMed  CAS  Google Scholar 

  • Ramezani A, Aghakhani A, Kalantar E, Banifazl M, Eslamifar A, Velayati AA (2009) HLA-A *3303* and *3301 predispose patients to persistent hepatitis B infection. J Gastrointestin Liver Dis 18:117–118

    PubMed  Google Scholar 

  • Rebmann V, van der Ven K, Passler M, Pfeiffer K, Krebs D, Grosse-Wilde H (2001) Association of soluble HLA-G plasma levels with HLA-G alleles. Tissue Antigens 57:15–21

    Article  PubMed  CAS  Google Scholar 

  • Robert-Gangneux F, Gangneux JP, Vu N, Jaillard S, Guiguen C, Amiot L (2011) High level of soluble HLA-G in amniotic fluid is correlated with congenital transmission of Toxoplasma gondii. Clin Immunol 138:129–134

    Article  PubMed  CAS  Google Scholar 

  • Robinson J, Mistry K, McWilliam H, Lopez R, Parham P, Marsh SG (2011) The IMGT/HLA database. Nucleic Acids Res 39:D1171–D1176

    Article  PubMed  Google Scholar 

  • Schulte D, Vogel M, Langhans B, Kramer B, Korner C, Nischalke HD, Steinberg V, Michalk M, Berg T, Rockstroh JK, Sauerbruch T, Spengler U, Nattermann J (2009) The HLA-E(R)/HLA-E(R) genotype affects the natural course of hepatitis C virus (HCV) infection and is associated with HLA-E-restricted recognition of an HCV-derived peptide by interferon-gamma-secreting human CD8(+) T cells. J Infect Dis 200:1397–1401

    Article  PubMed  CAS  Google Scholar 

  • Schutt P, Schutt B, Switala M, Bauer S, Stamatis G, Opalka B, Eberhardt W, Schuler M, Horn PA, Rebmann V (2010) Prognostic relevance of soluble human leukocyte antigen-G and total human leukocyte antigen class I molecules in lung cancer patients. Hum Immunol 71:489–495

    Article  PubMed  CAS  Google Scholar 

  • Segat L, Catamo E, Fabris A, Morgutti M, D'Agaro P, Campello C, Crovella S (2010) HLA-G*0105N allele is associated with augmented risk for HIV infection in white female patients. AIDS 24:1961–1964

    Article  PubMed  Google Scholar 

  • Souto FJ, Crispim JC, Ferreira SC, da Silva AS, Bassi CL, Soares CP, Zucoloto S, Rouas-Freiss N, Moreau P, Martinelli AL, Donadi EA (2010) Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection. J Viral Hepat 18(2):102–105

    Article  Google Scholar 

  • Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L, Solway J, Gern JE, Lemanske RF, Nicolae D, Ober C (2007) Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am J Hum Genet 81:829–834

    Article  PubMed  CAS  Google Scholar 

  • Tse KP, Su WH, Chang KP, Tsang NM, Yu CJ, Tang P, See LC, Hsueh C, Yang ML, Hao SP, Li HY, Wang MH, Liao LP, Chen LC, Lin SR, Jorgensen TJ, Chang YS, Shugart YY (2009) Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3. Am J Hum Genet 85:194–203

    Article  PubMed  CAS  Google Scholar 

  • Vince GS, Johnson PM (1995) Materno-fetal immunobiology in normal pregnancy and its possible failure in recurrent spontaneous abortion? Hum Reprod 10(Suppl 2):107–113

    PubMed  CAS  Google Scholar 

  • Yan WH, Fan LA, Yang JQ, Xu LD, Ge Y, Yao FJ (2006) HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortion. Int J Immunogenet 33:55–58

    Article  PubMed  CAS  Google Scholar 

  • Yie SM, Li LH, Xiao R, Librach CL (2008) A single base-pair mutation in the 3'-untranslated region of HLA-G mRNA is associated with pre-eclampsia. Mol Hum Reprod 14:649–653

    Article  PubMed  CAS  Google Scholar 

  • Zheng XQ, Zhu F, Sh WW, Lin A, Yan WH (2009) The HLA-G 14 bp insertion/deletion polymorphism is a putative susceptible factor for active human cytomegalovirus infection in children. Tissue Antigens 74:317–321

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Key Program of National Natural Science Foundation of China (no. 30730085), Scientific Research Fund of Zhejiang Provincial Education Department grant (no. Y200908541), and the National Basic Research Program of China (973 Program) (no. 2009CB522403). We thank Professor Martin F. Flajnik, Haiyang Xie, and Xiaobo Yu for their valuable assistance.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine Zhejiang University, 310003, Hangzhou, Zhejiang Province, People’s Republic of China

    Jian Zhang, Lelin Pan, Luyan Chen, Xiaowen Feng, Lin Zhou & Shusen Zheng

Authors
  1. Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lelin Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luyan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaowen Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shusen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shusen Zheng.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 104 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, J., Pan, L., Chen, L. et al. Non-classical MHC-Ι genes in chronic hepatitis B and hepatocellular carcinoma. Immunogenetics 64, 251–258 (2012). https://doi.org/10.1007/s00251-011-0580-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-011-0580-2

Keywords

Search

Navigation