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Clinical Rheumatology

, Volume 26, Issue 11, pp 1921–1924 | Cite as

Association of interferon-gamma gene polymorphism (+874A) with arthritis manifestation in SLE

  • Marut Tangwattanachuleeporn
  • Pimpayao Sodsai
  • Yingyos Avihingsanon
  • Jongkonnee Wongpiyabovorn
  • Jeerapat Wongchinsri
  • Nattiya Hirankarn
Brief Report

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which genetic factors strongly influence susceptibility. Cytokines such as the interferon-gamma (IFNG) gene play a key role in controlling the immunity and inflammation, and therefore their polymorphisms may affect these genes’ expression levels among individuals. We investigated the frequency of IFNG gene intron (+874) polymorphism, previously reported to be associated with IFNG production, in SLE patients compared to a control group. This population-based case–control study includes 154 SLE patients and 154 healthy control subjects with similar ethnic backgrounds. The genotyping was determined by polymerase chain reaction sequence-specific primer method and using the Chi-squared test for analyzing the association between this single-nucleotide polymorphism and SLE. The allele frequencies of the IFNG (+874) gene polymorphism were not significantly different between SLE patients and control subjects (72.7 vs 77%). However, there was a significant association between A dominance model of inheritance with arthritis (odds ratio = 7.64, 95% confidence interval = 1.56–41.64, P = 0.006, P c = 0.03). The result suggested that the +874 intron polymorphism of IFNG can be used as the marker for SLE susceptibility with arthritis in the Thai population.

Keywords

Interferon-gamma Polymorphisms SLE Thai population 

Notes

Acknowledgments

This study was supported by the Human Genetics grant from National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand, Ministry of University Affairs (MUA)–CU Thesis Grant 2002, and Lupus Research Unit, Chulalongkorn University. The authors wish to thank all the patients for their cooperation.

References

  1. 1.
    Baccala R, Kono DH, Theofilopoulos AN (2005) Interferons as pathogenic effectors in autoimmunity. Immunol Rev 204:9–26PubMedCrossRefGoogle Scholar
  2. 2.
    Csiszar A, Nagy G, Gergely P et al (2000) Increased interferon-gamma (IFN-gamma), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 122:464–470PubMedCrossRefGoogle Scholar
  3. 3.
    Lit LC, Wong CK, Tam LS et al (2006) Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus. Ann Rheum Dis 65:209–215PubMedCrossRefGoogle Scholar
  4. 4.
    Gomez D, Correa PA, Gomez LM et al (2004) Th1/Th2 cytokines in patients with systemic lupus erythematosus: is tumor necrosis factor alpha protective? Semin Arthritis Rheum 33:404–413PubMedCrossRefGoogle Scholar
  5. 5.
    al-Janadi M, al-Balla S, al-Dalaan A et al (1993) Cytokine profile in systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases. J Clin Immunol 13:58–67PubMedCrossRefGoogle Scholar
  6. 6.
    Adam C, Thoua Y, Ronco P et al (1980) The effect of exogenous interferon: acceleration of autoimmune and renal diseases in (NZB/W) F1 mice. Clin Exp Immunol 40:373–382PubMedGoogle Scholar
  7. 7.
    Amital H, Levi Y, Blank M et al (1998) Immunomodulation of murine experimental SLE-like disease by interferon-gamma. Lupus 7:445–454PubMedCrossRefGoogle Scholar
  8. 8.
    Jacob CO, Meide PH, McDevitt HO (1987) In vivo treatment of (NZB X NZW)F1 lupus-like nephritis with monoclonal antibody to gamma interferon. J Exp Med 166:798–803PubMedCrossRefGoogle Scholar
  9. 9.
    Akahoshi M, Nakashima H, Tanaka Y et al (1999) Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus. Arthritis Rheum 42:1644–1648PubMedCrossRefGoogle Scholar
  10. 10.
    Takahashi S, Fossati L, Iwamoto M et al (1996) Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. J Clin Invest 97:1597–604PubMedCrossRefGoogle Scholar
  11. 11.
    Funauchi M, Ikoma S, Enomoto H et al (1998) Decreased Th1-like and increased Th2-like cells in systemic lupus erythematosus. Scand J Rheumatol 27:219–224PubMedCrossRefGoogle Scholar
  12. 12.
    Min DJ, Cho ML, Cho CS et al (2001) Decreased production of interleukin-12 and interferon-gamma is associated with renal involvement in systemic lupus erythematosus. Scand J Rheumatol 30:159–163PubMedCrossRefGoogle Scholar
  13. 13.
    Jones BM, Liu T, Wong RW (1999) Reduced in vitro production of interferon-gamma, interleukin-4 and interleukin-12 and increased production of interleukin-6, interleukin-10 and tumour necrosis factor-alpha in systemic lupus erythematosus. Weak correlations of cytokine production with disease activity. Autoimmunity 31:117–124PubMedCrossRefGoogle Scholar
  14. 14.
    Horwitz DA, Gray JD, Behrendsen SC et al (1998) Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus. Arthritis Rheum 41:838–844PubMedCrossRefGoogle Scholar
  15. 15.
    Nicoletti F, Di Marco R, Zaccone P et al (2000) Dichotomic effects of IFN-gamma on the development of systemic lupus erythematosus-like syndrome in MRL-lpr/lpr mice. Eur J Immunol 30:438–447PubMedCrossRefGoogle Scholar
  16. 16.
    Pravica V, Asderakis A, Perrey C et al (1999) In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene. Eur J Immunogenet 26(1):1–3PubMedCrossRefGoogle Scholar
  17. 17.
    Pravica V, Perrey C, Stevens A et al (2000) A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol 61(9):863–866PubMedCrossRefGoogle Scholar
  18. 18.
    Lee JY, Goldman D, Piliero LM et al (2004) Interferon-gamma polymorphisms in systemic lupus erythematosus. Genes Immun 2(5):254–257CrossRefGoogle Scholar
  19. 19.
    Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215PubMedCrossRefGoogle Scholar
  20. 20.
    Awad M, Pravica V, Perrey C et al (1999) CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis. Hum Immunol 60(4):343–346PubMedCrossRefGoogle Scholar
  21. 21.
    Dean AG, Dean JA, Burton AH et al (1991) Epi Info: a general-purpose microcomputer program for public health information systems. Am J Prev Med 7(3):178–182PubMedGoogle Scholar
  22. 22.
    Nakashima H, Inoue H, Akahoshi M et al (1999) The combination of polymorphisms within interferon-gamma receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus. FEBS Lett 453(1–2):187–190PubMedCrossRefGoogle Scholar
  23. 23.
    Tanaka Y, Nakashima H, Hisano C et al (1999) Association of the interferon-gamma receptor variant (Val14Met) with systemic lupus erythematosus. Immunogenetics 49(4):266–271PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2007

Authors and Affiliations

  • Marut Tangwattanachuleeporn
    • 1
    • 2
  • Pimpayao Sodsai
    • 1
    • 2
  • Yingyos Avihingsanon
    • 1
    • 3
  • Jongkonnee Wongpiyabovorn
    • 1
    • 4
  • Jeerapat Wongchinsri
    • 5
  • Nattiya Hirankarn
    • 1
    • 4
  1. 1.Lupus Research Unit, Department of Microbiology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  2. 2.Inter-department of Medical Microbiology, Graduate SchoolChulalongkorn UniversityBangkokThailand
  3. 3.Department of Medicine, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  4. 4.Department of Microbiology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  5. 5.Department of MedicineNopparat Rajathanee HospitalBangkokThailand

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