Content-Length: 332540 | pFad | https://doi.org/10.1007/s00251-009-0377-8

a=86400 A regulatory polymorphism in interferon-γ receptor 1 promoter is associated with the susceptibility to chronic hepatitis B virus infection | Immunogenetics Skip to main content
Springer Nature Link
Log in

A regulatory polymorphism in interferon-γ receptor 1 promoter is associated with the susceptibility to chronic hepatitis B virus infection

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The antiviral cascade triggered by interferon-γ (IFN-γ) represents a vital event for eradicating hepatitis B virus (HBV) in experimental animals. IFN-γ signaling is mediated through the ligand binding to IFN-γ receptor 1 (IFNGR1). Control of IFNGR1 expression level is one of the mechanisms by which cells modulate the potency of IFN-γ signaling. In this study, we comprehensively investigated the single nucleotide polymorphisms (SNPs) in IFNGR1 gene and correlated their occurrence to susceptibility to HBV infection in a Chinese population. A total of 983 participants, including 361 chronic hepatitis B patients, 256 individuals who had spontaneously recovered from HBV infection, and 366 healthy control subjects, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism was used to identify seven SNPs (–611A/G, –56C/T, 40G/A, 95C/T, 130A/G, 20685A/G, 21227T/C) in IFNGR1 gene. We found that –56C and –56T allele were associated with viral clearance and viral persistence, respectively (P = 0.014). In a reporter-driven assay, we validated that the promoter variant with –56C exhibited a higher transcription level than that with –56T in HepG2 cells in a cell-type-specific pattern. We conclude that a functional –56C/T SNP in IFNGR1 promoter is associated with the clinical outcome of HBV infection in this Chinese population.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

IFN-γ:

Interferon-γ

IFNGR1:

IFN-γ receptor 1

HBV:

Hepatitis B virus

SNP:

Single nucleotide polymorphism

CHP:

Chronic hepatitis B patients

SRI:

Spontaneous recovered individuals

HCS:

Healthy control subjects

PCR-RFLP:

Polymerase chain reaction-restriction fragment length polymorphism

LD:

Linkage disequilibrium

References

  • Abbott W, Gane E, Winship I, Munn S, Tukuitonga C (2007) Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians. Immunogenetics 59:187–195. doi:10.1007/s00251-006-0184-4

    Article  PubMed  CAS  Google Scholar 

  • Aoki M, Matsui E, Kaneko H, Inoue R, Fukao T, Watanabe M, Teramoto T, Kato Z, Suzuki K, Suzuki Y, Kasahara K, Kondo N (2003) A novel single-nucleotide substitution, Leu 467 Pro, in the interferon-gamma receptor 1 gene associated with allergic diseases. Int J Mol Med 12:185–191

    PubMed  CAS  Google Scholar 

  • Basturk B, Karasu Z, Kilic M, Ulukaya S, Boyacioglu S, Oral B (2008) Association of TNF-alpha -308 polymorphism with the outcome of hepatitis B virus infection in Turkey. Infect Genet Evol 8:20–25. doi:10.1016/j.meegid.2007.09.001

    Article  PubMed  CAS  Google Scholar 

  • Ben-Ari Z, Mor E, Papo O, Kfir B, Sulkes J, Tambur AR, Tur-Kaspa R, Klein T (2003) Cytokine gene polymorphisms in patients infected with hepatitis B virus. Am J Gastroenterol 98:144–150. doi:10.1111/j.1572-0241.2003.07179.x

    Article  PubMed  CAS  Google Scholar 

  • Bulat-Kardum L, Etokebe GE, Knezevic J, Balen S, Matakovic-Mileusnic N, Zaputovic L, Pavelic J, Beg-Zec Z, Dembic Z (2006) Interferon-gamma receptor-1 gene promoter polymorphisms (G–611A; T–56C) and susceptibility to tuberculosis. Scand J Immunol 63:142–150. doi:10.1111/j.1365-3083.2005.01694.x

    Article  PubMed  CAS  Google Scholar 

  • Chen GY, Chen Z, Li MW, Liu HM, Hu ZR (2003) Modulation and implications in pathogenesis of interferon gamma receptor 1 in patients with chronic hepatitis B. Zhonghua Gan Zang Bing Za Zhi 11:14–16

    PubMed  CAS  Google Scholar 

  • Cheong JY, Cho SW, Chung SG, Lee JA, Yeo M, Wang HJ, Lee JE, Hahm KB, Kim JH (2006) Genetic polymorphism of interferon-gamma, interferon-gamma receptor, and interferon regulatory factor-1 genes in patients with hepatitis B virus infection. Biochem Genet 44:246–255. doi:10.1007/s10528-006-9029-y

    Article  PubMed  CAS  Google Scholar 

  • Cooke GS, Campbell SJ, Sillah J, Gustafson P, Bah B, Sirugo G, Bennett S, McAdam KP, Sow O, Lienhardt C, Hill AV (2006) Polymorphism within the interferon-gamma/receptor complex is associated with pulmonary tuberculosis. Am J Respir Crit Care Med 174:339–343. doi:10.1164/rccm.200601-088OC

    Article  PubMed  CAS  Google Scholar 

  • Deng G, Zhou G, Zhai Y, Li S, Li X, Li Y, Zhang R, Yao Z, Shen Y, Qiang B, Wang Y, He F (2004) Association of estrogen receptor alpha polymorphisms with susceptibility to chronic hepatitis B virus infection. Hepatology 40:318–326. doi:10.1002/hep.20318

    Article  PubMed  CAS  Google Scholar 

  • Du T, Guo XH, Zhu XL, Li JH, Lu LP, Gao JR, Gou CY, Li Z, Liu Y, Li H (2006) Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population. J Viral Hepatitis 13:618–624. doi:10.1111/j.1365-2893.2006.00731.x

    Article  CAS  Google Scholar 

  • Frodsham AJ, Zhang L, Dumpis U, Taib NA, Best S, Durham A, Hennig BJ, Hellier S, Knapp S, Wright M, Chiaramonte M, Bell JI, Graves M, Whittle HC, Thomas HC, Thursz MR, Hill AV (2006) Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. Proc Natl Acad Sci U S A 103:9148–9153. doi:10.1073/pnas.0602800103

    Article  PubMed  CAS  Google Scholar 

  • Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber R, Chisari FV (1996) Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4:25–36. doi:10.1016/S1074-7613(00)80295-2

    Article  PubMed  CAS  Google Scholar 

  • Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV (1999) Viral clearance without destruction of infected cells during acute HBV infection. Science 284:825–829. doi:10.1126/science.284.5415.825

    Article  PubMed  CAS  Google Scholar 

  • Hohler T, Kruger A, Gerken G, Schneider PM, Buschenefelde KH Meyer zum, Rittner C (1998) A tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism is associated with chronic hepatitis B infection. Clin Exp Immunol 111:579–582. doi:10.1046/j.1365-2249.1998.00534.x

    Article  PubMed  CAS  Google Scholar 

  • Juliger S, Bongartz M, Luty AJ, Kremsner PG, Kun JF (2003) Functional analysis of a promoter variant of the gene encoding the interferon-gamma receptor chain I. Immunogenetics 54:675–680

    PubMed  Google Scholar 

  • Kim YJ, Lee HS, Yoon JH, Kim CY, Park MH, Kim LH, Park BL, Shin HD (2003) Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. Hum Mol Genet 12:2541–2546. doi:10.1093/hmg/ddg262

    Article  PubMed  CAS  Google Scholar 

  • Knight JC, Udalova I, Hill AV, Greenwood BM, Peshu N, Marsh K, Kwiatkowski D (1999) A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet 22:145–150. doi:10.1038/9649

    Article  PubMed  CAS  Google Scholar 

  • Koch O, Awomoyi A, Usen S, Jallow M, Richardson A, Hull J, Pinder M, Newport M, Kwiatkowski D (2002) IFNGR1 gene promoter polymorphisms and susceptibility to cerebral malaria. J Infect Dis 185:1684–1687. doi:10.1086/340516

    Article  PubMed  CAS  Google Scholar 

  • Koch O, Kwiatkowski DP, Udalova IA (2006) Context-specific functional effects of IFNGR1 promoter polymorphism. Hum Mol Genet 15:1475–1481. doi:10.1093/hmg/ddl071

    Article  PubMed  CAS  Google Scholar 

  • Liu M, Cao B, Zhang H, Dai Y, Liu X, Xu C (2006) Association of interferon-gamma gene haplotype in the Chinese population with hepatitis B virus infection. Immunogenetics 58:859–864. doi:10.1007/s00251-006-0161-y

    Article  PubMed  CAS  Google Scholar 

  • Matsuda A, Ebihara N, Kumagai N, Fukuda K, Ebe K, Hirano K, Sotozono C, Tei M, Hasegawa K, Shimizu M, Tamari M, Namba K, Ohno S, Mizuki N, Ikezawa Z, Shirakawa T, Hamuro J, Kinoshita S (2007) Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts. Invest Ophthalmol Vis Sci 48:583–589. doi:10.1167/iovs.06-0991

    Article  PubMed  Google Scholar 

  • Novelli F, Bernabei P, Ozmen L, Rigamonti L, Allione A, Pestka S, Garotta G, Forni G (1996) Switching on of the proliferation or apoptosis of activated human T lymphocytes by IFN-gamma is correlated with the differential expression of the alpha- and beta-chains of its receptor. J Immunol 157:1935–1943

    PubMed  CAS  Google Scholar 

  • Rosenzweig SD, Schaffer AA, Ding L, Sullivan R, Enyedi B, Yim JJ, Cook JL, Musser JM, Holland SM (2004) Interferon-gamma receptor 1 promoter polymorphisms: population distribution and functional implications. Clin Immunol 112:113–119. doi:10.1016/j.clim.2004.03.018

    Article  PubMed  CAS  Google Scholar 

  • Suneetha PV, Sarin SK, Goyal A, Kumar GT, Shukla DK, Hissar S (2006) Association between vitamin D receptor, CCR5, TNF-alpha and TNF-beta gene polymorphisms and HBV infection and severity of liver disease. J Hepatol 44:856–863. doi:10.1016/j.jhep. 2006.01.028

    Article  PubMed  CAS  Google Scholar 

  • Tanaka Y, Nakashima H, Hisano C, Kohsaka T, Nemoto Y, Niiro H, Otsuka T, Otsuka T, Imamura T, Niho Y (1999) Association of the interferon-gamma receptor variant (Val14Met) with systemic lupus erythematosus. Immunogenetics 49:266–271. doi:10.1007/s002510050492

    Article  PubMed  CAS  Google Scholar 

  • Tau G, Rothman P (1999) Biologic functions of the IFN-gamma receptors. Allergy 54:1233–1251. doi:10.1034/j.1398-9995.1999.00099.x

    Article  PubMed  CAS  Google Scholar 

  • Thio CL, Thomas DL, Karacki P, Gao X, Marti D, Kaslow RA, Goedert JJ, Hilgartner M, Strathdee SA, Duggal P, O’Brien SJ, Astemborski J, Carrington M (2003) Comprehensive analysis of class I and class II HLA antigens and chronic hepatitis B virus infection. J Virol 77:12083–12087. doi:10.1128/JVI.77.22.12083-12087.2003

    Article  PubMed  CAS  Google Scholar 

  • Wieland S, Thimme R, Purcell RH, Chisari FV (2004) Genomic analysis of the host response to hepatitis B virus infection. Proc Natl Acad Sci U S A 101:6669–6674. doi:10.1073/pnas.0401771101

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Lu L, Yuen MF, Lam TW, Chung CP, Lam CL, Zhang B, Wang S, Chen Y, Wu SH, Poon VK, Ng F, Chan CC, Jiang S, Yuen KY, Zheng BJ (2007) Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection. J Hepatol 46:198–205. doi:10.1016/j.jhep. 2006.08.017

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This work was supported in part by the University Development Fund of the University of Hong Kong.

Author information

Author notes

  1. Jie Zhou

    Present address: Northern California Institute for Research and Education, San Francisco, CA, USA

Authors and Affiliations

  1. Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong SAR, China

    Jie Zhou, Ding-Qiang Chen, Vincent K. M. Poon, Yong Zeng, Fai Ng, Kwok-Yung Yuen & Bo-Jian Zheng

  2. Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China

    Liwei Lu, Kwok-Yung Yuen & Bo-Jian Zheng

  3. Department of Pathology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China

    Liwei Lu

  4. Department of Biochemistry, The University of Hong Kong, Hong Kong, Hong Kong SAR, China

    Jian-Dong Huang

Authors
  1. Jie Zhou
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Ding-Qiang Chen
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Vincent K. M. Poon
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Yong Zeng
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Fai Ng
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Liwei Lu
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Jian-Dong Huang
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Kwok-Yung Yuen
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Bo-Jian Zheng
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Bo-Jian Zheng.

Additional information

J. Zhou and D.-Q. Chen contributed to this study equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, J., Chen, DQ., Poon, V.K.M. et al. A regulatory polymorphism in interferon-γ receptor 1 promoter is associated with the susceptibility to chronic hepatitis B virus infection. Immunogenetics 61, 423–430 (2009). https://doi.org/10.1007/s00251-009-0377-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-009-0377-8

Keywords









 ApplySandwichStrip

pFad - (p)hone/(F)rame/(a)nonymizer/(d)eclutterfier!      Saves Data!


--- a PPN by Garber Painting Akron. With Image Size Reduction included!

Fetched URL: https://doi.org/10.1007/s00251-009-0377-8

Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy