Journal of Dermatological Science
Volume 30, Issue 2 , Pages 161-166 , November 2002

Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris

  • Yuichiro Tsunemi

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81-3-5800-8661; fax: +81-3-3814-1503
    • ,
  • Hidehisa Saeki

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Koichiro Nakamura

      Affiliations

    • Department of Dermatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima city, Fukushima 960-1295, Japan
    • ,
  • Takashi Sekiya

      Affiliations

    • Department of Allergy and Rheumatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Koichi Hirai

      Affiliations

    • Department of Allergy and Rheumatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Hideki Fujita

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Noriko Asano

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Megumi Kishimoto

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Yuka Tanida

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Takashi Kakinuma

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Hiroshi Mitsui

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Yayoi Tada

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Motoshi Wakugawa

      Affiliations

    • Department of Dermatology, University of Teikyo Mizonokuchi Hospital, 3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki city, Kanagawa 213-8507, Japan
    • ,
  • Hideshi Torii

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Mayumi Komine

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Akihiko Asahina

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Kunihiko Tamaki

      Affiliations

    • Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

Received 2 May 2002 ,Revised 3 July 2002 ,Accepted 10 July 2002.

References 

  1. Kiniwa M, Gately M, Gubler U, Chizzonite R, Fargeas C, Delespesse G. Recombinant interleukin-12 suppresses the synthesis of immunoglobulin E by interleukin-4 stimulated human lymphocytes. J. Clin. Invest. 1992;90:262–266
  2. Morris SC, Madden KB, Adamovicz JJ, Cause WC, Hubbard BR, Gately MK, et al. Effect of IL-12 on in vivo cytokine gene expression and Ig isotype selection. J. Immunol. 1994;152:1047–1056
  3. Ma X, Aste-Amezaga M, Gri G, Gerosa F, Trinchieri G. Immunomodulatory functions and molecular regulation of IL-12. Chem. Immunol. 1997;68:1–22
  4. Trinchieri G. Interleukin-12:a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol. 1995;13:251–276
  5. Germann T, Gately MK, Schoenhaut DS, Lohoff M, Mattner F, Fischer S, et al. Interleukin-12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells. Eur. J. Immunol. 1993;23:1762–1770
  6. MacKnight AJ, Zimmer GJ, Fogelman I, Wolf SF, Abbas AK. Effects of IL-12 on helper T cell-dependent immune responses in vivo. J. Immunol. 1994;152:2172–2179
  7. Trembleau S, Germann T, Gately MK, Adorini L. The role of IL-12 in the induction of organ-specific autoimmune diseases. Immunol. Today. 1995;16:383–386
  8. Wu CY, Demeure C, Kiniwa M, Gately M, Delespesse G. IL-12 induces the production of IFN-γ by neonatal human CD4 T cells. J. Immunol. 1993;151:1938–1949
  9. Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, et al. Natural killer cell stimulatory factor (Interleukin12 [IL-12])induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4 producing Th cells. J. Exp. Med. 1993;177:1199–1204
  10. Hamid Q, Bogunieewicz M, Leung DYM. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J. Clin. Invest. 1994;94:870–876
  11. van der Heijden FL, Wierenga EA, Bos JD, Kapsenberg ML. High frequency of IL-4-producing CD4+ allergen-specific T lymphocytes in atopic dermatitis lesional skin. J. Invest. Dermatol. 1991;97:389–394
  12. Grewe M, Bruijnzeel-Koomen CAFM, Schöpf E, Thepen T, Langeveld-Wildschut AG, Ruzicka T, et al. A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunol. Today. 1998;19:359–361
  13. Schlaak JF, Buslau M, Jochum W, Hermann E, Girndt M, Gallati H, et al. T cells involved in psoriasis vulgaris belong to the Th1 subset. J. Invest. Dermatol. 1994;102:145–149
  14. Uyemura K, Yamamura M, Fivenson DF, Modlin RL, Nickoloff BJ. The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type1 cell-mediated responses. J. Invest. Dermatol. 1993;101:701–705
  15. Hall MA, McGlinn E, Coakley G, Fisher SA, Boki K, Middleton D, et al. Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. Genes Immun. 2000;1:219–224
  16. Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J. Immunol. 1991;146:3074–3081
  17. Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, et al. Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc. Natl. Acad. Sci. USA. 1991;88:4143–4147
  18. Huang D, Cancilla MR, Morahan G. Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Genes Immun. 2000;1:515–520
  19. Warrington JA, Bengtsson U. High-resolution physical mapping of human 5q31–q33 using three methods: radiation hybrid mapping, interphase fluorescence in situ hybridization, and pulsed-field gel electrophoresis. Genomics. 1994;24:395–398
  20. Forrest S, Dunn K, Elliott K, Fitzpatrick E, Fullerton J, McCarthy M, et al. Identifying genes predisposing to atopic eczema. J. Allergy Clin. Immunol. 1999;104:1066–1070
  21. Beyer K, Nickel R, Freidhoff L, Björkstén B, Huang SK, Barnes KC, et al. Association and linkage of atopic dermatitis with chromosome 13q12–14 and 5q31–33 markers. J. Invest. Dermatol. 2000;115:906–908
  22. Söderhäll C, Bradley M, Kockum I, Wahlgren CF, Luthman H, Nordenskjöld M. Linkage and association to candidate regions in Swedish atopic dermatitis families. Hum. Genet. 2001;109:129–135
  23. Morahan G, Huang D, Ymer SI, Cancilla MR, Stephen K, Dabadghao P, et al. Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat. Genet. 2001;27:218–221
  24. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm. Venereol. Suppl. 1980;92:44–47
  25. Toussaint S, Kamino H. Psoriasis. In:  Elder D,  Elentisas R,  Jawprsky C,  Johnson B editor. Lever's histopathology of the skin. 8th ed.. Philadelphia, PA: Lippincott-Raven Publishers; 1997;p. 156–163
  26. Bette M, Jin SC, Germann T, Schäfer MKH, Weihe E, Rüde E, et al. Differential expression of m RNA encoding interleukin-12 p35 and p40 subunits in situ. Eur. J. Immunol. 1994;24:2435–2440
  27. D'Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferonγ-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. Exp. Med. 1993;178:1041–1048
  28. Grewe M, Gyufko K, Schöpf E, Krutmann J. Lesional expression of interferon-γ in atopic eczema. Lancet. 1994;343:25–26
  29. Snijders A, van der Pouw Kraan TCTM, Engel M, Wormmeester J, Widjaja P, Zonneveld IM, et al. Enhanced prostaglandin E2 production by monocytes in atopic dermatitis (AD) is not accompanied by enhanced production of IL-6, IL-10 or IL-12. Clin. Exp. Immunol. 1998;111:472–476
  30. König B, Neuber K, König W. Responsiveness of peripheral blod mononuclear cells from normal and aoic donors to microbial superantigens. Int. Arch. Allergy Immunol. 1995;106:124–133
  31. Yawalker N, Karlen S, Hunger R, Brand CU, Braathen LR. Expression of interleukin-12 is increased in psoriatic skin. J. Invest. Dermatol. 1998;111:1053–1057
  32. Hong K, Chu A, Ludviksson BR, Berg EL, Ehrhardt RO. IL-12, independently of IFN-γ, plays a crucial role in the pathogenesis of a murine psoriasis-like sin disorder. J. Immunol. 1999;162:7480–7490
  33. Nickel RG, Casolaro V, Wahn U, Beyer K, Barnes KC, Plunkett BS, et al. Atopic dermatitis is associated with a functional mutation in the promoter of the C–C chemokine RANTES. J. Immunol. 2000;164:1612–1616
  34. Khurana-Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA. The association of atopy with a gain-of-function mutaion in the a subunit of the interleukin-4 receptor. N. Engl. J. Med. 1997;337:1720–1725
  35. Mitsuyasu H, Yanagihara Y, Mao XQ, Gao PS, Arinobu Y, Ihara K, et al. Dominant effect of Ile 50 Val variant of the human IL-4 receptor a-chain in IgE synthesis. J. Immunol. 1999;162:1227–1231
  36. Kawashima T, Noguchi E, Arinami T, Yamakawa-Kobayashi K, Nakagawa H, Otsuka F, et al. Linkage and association of an interleukin 4 gene polymorphism with atopic dermatitis in Japanese families. J. Med. Genet. 1998;35:502–504
  37. Liu X, Nickel R, Beyer K, Wahn U, Ehrlich E, Freidhoff LR, et al. An IL 13 coding resion variant is associated with a high total serum IgE level and atopic dermatitis in the German multicenter atopy study (MAS-90). J. Allergy Clin. Immunol. 2000;106:167–170
  38. Oiso N, Fukai K, Ishii M. Interleukin 4 receptor a chain polymorphism Gln 551 Arg is associated with adult atopic dermatitis in Japan. Br. J. Dermatol. 2000;142:1003–1006
  39. Cox HE, Moffatt MF, Faux JA, Walley AJ, Coleman R, Trembath RC, et al. Association of atopic dermatitis to the beta subunit of the high affinity immunoglobulin E receptor. Br. J. Dermatol. 1998;138:182–187
  40. Höhler T, Kruger A, Schneider PM, Schopf RE, Knop J, Rittner C, et al. A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis. J. Invest. Dermatol. 1997;109:562–565
  41. Cookson WOCM, Ubhi B, Lawrence R, Abecasis GR, Walley AJ, Cox HE, et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat. Genet. 2001;27:372–373
  42. Noguchi E, Yokouchi Y, Shibasaki M, Kamioka M, Yamakawa-Kobayashi K, Matsui A, et al. Identification of missense mutation in the IL12B gene: lack of association between IL12B polymorphisms and asthma and allergic rhinitis in the Japanese population. Genes Immun. 2001;2:401–403
  43. Dahlman I, Eaves IA, Kosoy R, Morrison VA, Heward J, Gough SC, et al. Parameters for reliable results in genetic association studies in common disease. Nat Genet. 2002;30:50–149

PII: S0923-1811(02)00072-5

Journal of Dermatological Science
Volume 30, Issue 2 , Pages 161-166 , November 2002

Article Tools