Skip to main content
SpringerLink
Log in

Meta-analysis of IL12B polymorphisms (rs3212227, rs6887695) with psoriasis and psoriatic arthritis

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Interleukin 12 (IL-12) is a key player in model systems of autoimmunity. One of the most robust genetic findings is the association of variants in the IL12B gene with psoriasis and psoriatic arthritis (PsA). This study aims to assess whether combined evidence shows the association between IL12B polymorphisms and the susceptibility to psoriasis/PsA. We conducted a systematic review to examine the association between the IL12B rs3212227 (1188A > C) and rs6887695 and psoriasis/PsA. In addition, we used studies for which combined information from all genotypes was available to compare risks in dominant and recessive model. Potential publication bias was evaluated by Egger’s linear regression test. Eleven articles met the inclusion criteria and contributed data to the meta-analyses. For rs3212227, the odds ratios the minor allele for psoriasis and PsA were 0.688 (95 % CI 0.650–0.729) and 0.707 (95 % CI 0.628–0.797), respectively. Then, for rs6887695, the pooled ORs were 0.704 (95 % CI 0.670–0.739) for psoriasis and 0.677 (95 % CI 0.599–0.767) for PsA. The overall ORs for all genotypes of rs3212227 and rs6887695 were all significantly associated with psoriasis. No publication bias was presented. Taken together, our results demonstrate a significant association between IL12B gene polymorphisms and psoriasis and PsA.

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

Similar content being viewed by others

References

  1. Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361(5):496–509. doi:10.1056/NEJMra0804595

    Article  PubMed  CAS  Google Scholar 

  2. Gladman DD, Antoni C, Mease P, Clegg DO, Nash P (2005) Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 64(Suppl 2:ii):14–17. doi:10.1136/ard.2004.032482

    Google Scholar 

  3. Hall MA, McGlinn E, Coakley G, Fisher SA, Boki K, Middleton D, Kaklamani E, Moutsopoulos H, Loughran TP Jr, Ollier WE, Panayi GS, Lanchbury JS (2000) Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. Genes Immun 1(3):219–224. doi:10.1038/sj.gene.6363661

    Article  PubMed  CAS  Google Scholar 

  4. Zheng HF, Zuo XB, Lu WS, Li Y, Cheng H, Zhu KJ, Yin XY, Zhang C, Ren YQ, Wang WJ, Sun LD, Cui Y, Yang S, Zhang FY, Zhang XJ (2011) Variants in MHC, LCE and IL12B have epistatic effects on psoriasis risk in Chinese population. J Dermatol Sci 61(2):124–128. doi:10.1016/j.jdermsci.2010.12.001

    Article  PubMed  CAS  Google Scholar 

  5. Duffin KC, Krueger GG (2009) Genetic variations in cytokines and cytokine receptors associated with psoriasis found by genome-wide association. J Invest Dermatol 129(4):827–833. doi:10.1038/jid.2008.308

    Article  PubMed  CAS  Google Scholar 

  6. Nair RP, Ruether A, Stuart PE, Jenisch S, Tejasvi T, Hiremagalore R, Schreiber S, Kabelitz D, Lim HW, Voorhees JJ, Christophers E, Elder JT, Weichenthal M (2008) Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J Invest Dermatol 128(7):1653–1661. doi:10.1038/sj.jid.5701255

    Article  PubMed  CAS  Google Scholar 

  7. Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A, Malloy MJ, Pullinger CR, Kane JP, Saccone S, Worthington J, Bruce I, Kwok PY, Menter A, Krueger J, Barton A, Saccone NL, Bowcock AM (2008) A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4(3):e1000041. doi:10.1371/journal.pgen.1000041

    Article  PubMed  Google Scholar 

  8. Filer C, Ho P, Smith RL, Griffiths C, Young HS, Worthington J, Bruce IN, Barton A (2008) Investigation of association of the IL12B and IL23R genes with psoriatic arthritis. Arthritis Rheum 58(12):3705–3709. doi:10.1002/art.24128

    Article  PubMed  CAS  Google Scholar 

  9. Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80(2):273–290. doi:10.1086/511051

    Article  PubMed  CAS  Google Scholar 

  10. Capon F, Di Meglio P, Szaub J, Prescott NJ, Dunster C, Baumber L, Timms K, Gutin A, Abkevic V, Burden AD, Lanchbury J, Barker JN, Trembath RC, Nestle FO (2007) Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum Genet 122(2):201–206. doi:10.1007/s00439-007-0397-0

    Article  PubMed  CAS  Google Scholar 

  11. Litjens NH, van der Plas MJ, Ravensbergen B, Numan-Ruberg SC, van Assen Y, Thio HB, van Dissel JT, van de Vosse E, Nibbering PH (2004) Psoriasis is not associated with IL-12p70/IL-12p40 production and IL12B promoter polymorphism. J Invest Dermatol 122(4):923–926. doi:10.1111/j.0022-202X.2004.22427.x

    Article  PubMed  CAS  Google Scholar 

  12. Tsunemi Y, Saeki H, Nakamura K, Sekiya T, Hirai K, Fujita H, Asano N, Kishimoto M, Tanida Y, Kakinuma T, Mitsui H, Tada Y, Wakugawa M, Torii H, Komine M, Asahina A, Tamaki K (2002) Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J Dermatol Sci 30(2):161–166

    Article  PubMed  CAS  Google Scholar 

  13. Huffmeier U, Uebe S, Ekici AB, Bowes J, Giardina E, Korendowych E, Juneblad K, Apel M, McManus R, Ho P, Bruce IN, Ryan AW, Behrens F, Lascorz J, Bohm B, Traupe H, Lohmann J, Gieger C, Wichmann HE, Herold C, Steffens M, Klareskog L, Wienker TF, Fitzgerald O, Alenius GM, McHugh NJ, Novelli G, Burkhardt H, Barton A, Reis A (2010) Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet 42(11):996–999. doi:10.1038/ng.688

    Article  PubMed  Google Scholar 

  14. Zhang XJ, Huang W, Yang S, Sun LD, Zhang FY, Zhu QX, Zhang FR, Zhang C, Du WH, Pu XM, Li H, Xiao FL, Wang ZX, Cui Y, Hao F, Zheng J, Yang XQ, Cheng H, He CD, Liu XM, Xu LM, Zheng HF, Zhang SM, Zhang JZ, Wang HY, Cheng YL, Ji BH, Fang QY, Li YZ, Zhou FS, Han JW, Quan C, Chen B, Liu JL, Lin D, Fan L, Zhang AP, Liu SX, Yang CJ, Wang PG, Zhou WM, Lin GS, Wu WD, Fan X, Gao M, Yang BQ, Lu WS, Zhang Z, Zhu KJ, Shen SK, Li M, Zhang XY, Cao TT, Ren W, Zhang X, He J, Tang XF, Lu S, Yang JQ, Zhang L, Wang DN, Yuan F, Yin XY, Huang HJ, Wang HF, Lin XY, Liu JJ (2009) Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 41(2):205–210. doi:10.1038/ng.310

    Article  PubMed  CAS  Google Scholar 

  15. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, Gudjonsson JE, Li Y, Tejasvi T, Feng BJ, Ruether A, Schreiber S, Weichenthal M, Gladman D, Rahman P, Schrodi SJ, Prahalad S, Guthery SL, Fischer J, Liao W, Kwok PY, Menter A, Lathrop GM, Wise CA, Begovich AB, Voorhees JJ, Elder JT, Krueger GG, Bowcock AM, Abecasis GR (2009) Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 41(2):199–204. doi:10.1038/ng.311

    Article  PubMed  CAS  Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634. doi:10.1136/bmj.315.7109.629

    Article  PubMed  CAS  Google Scholar 

  17. Smith RL, Warren RB, Eyre S, Ho P, Ke X, Young HS, Griffiths CE, Worthington J (2008) Polymorphisms in the IL-12beta and IL-23R genes are associated with psoriasis of early onset in a UK cohort. J Invest Dermatol 128(5):1325–1327. doi:10.1038/sj.jid.5701140

    Article  PubMed  CAS  Google Scholar 

  18. Wu Y, Lu Z, Chen Y, Xue F, Chen X, Zheng J (2010) Replication of association between interleukin-23 receptor (IL-23R) and its ligand (IL-12B) polymorphisms and psoriasis in the Chinese Han population. Hum Immunol 71(12):1255–1258. doi:10.1016/j.humimm.2010.09.014

    Article  PubMed  CAS  Google Scholar 

  19. Nair RP, Stuart PE, Kullavanijaya P, Tejasvi T, Voorhees JJ, Elder JT (2010) Genetic evidence for involvement of the IL23 pathway in Thai psoriatics. Arch Dermatol Res 302(2):139–143. doi:10.1007/s00403-009-0986-y

    Article  PubMed  CAS  Google Scholar 

  20. Huffmeier U, Lascorz J, Bohm B, Lohmann J, Wendler J, Mossner R, Reich K, Traupe H, Kurrat W, Burkhardt H, Reis A (2009) Genetic variants of the IL-23R pathway: association with psoriatic arthritis and psoriasis vulgaris, but no specific risk factor for arthritis. J Invest Dermatol 129(2):355–358. doi:10.1038/jid.2008.233

    Article  PubMed  Google Scholar 

  21. Chang YT, Chou CT, Yu CW, Lin MW, Shiao YM, Chen CC, Huang CH, Lee DD, Liu HN, Wang WJ, Tsai SF (2007) Cytokine gene polymorphisms in Chinese patients with psoriasis. Br J Dermatol 156(5):899–905. doi:10.1111/j.1365-2133.2007.07820.x

    Article  PubMed  CAS  Google Scholar 

  22. Griffiths CE, Barker JN (2007) Pathogenesis and clinical features of psoriasis. Lancet 370(9583):263–271. doi:10.1016/S0140-6736(07)61128-3

    Article  PubMed  CAS  Google Scholar 

  23. Di Cesare A, Di Meglio P, Nestle FO (2009) The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 129(6):1339–1350. doi:10.1038/jid.2009.59

    Article  PubMed  Google Scholar 

  24. Krueger GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, Wang Y, Dooley LT, Lebwohl M (2007) A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 356(6):580–592. doi:10.1056/NEJMoa062382

    Article  PubMed  CAS  Google Scholar 

  25. Ellinghaus E, Ellinghaus D, Stuart PE, Nair RP, Debrus S, Raelson JV, Belouchi M, Fournier H, Reinhard C, Ding J, Li Y, Tejasvi T, Gudjonsson J, Stoll SW, Voorhees JJ, Lambert S, Weidinger S, Eberlein B, Kunz M, Rahman P, Gladman DD, Gieger C, Wichmann HE, Karlsen TH, Mayr G, Albrecht M, Kabelitz D, Mrowietz U, Abecasis GR, Elder JT, Schreiber S, Weichenthal M, Franke A (2010) Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet 42(11):991–995. doi:10.1038/ng.689

    Article  PubMed  CAS  Google Scholar 

  26. Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, Barton A, Band G, Bellenguez C, Bergboer JG, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Cork MJ, Corvin A, Deloukas P, Dilthey A, Duncanson A, Edkins S, Estivill X, Fitzgerald O, Freeman C, Giardina E, Gray E, Hofer A, Huffmeier U, Hunt SE, Irvine AD, Jankowski J, Kirby B, Langford C, Lascorz J, Leman J, Leslie S, Mallbris L, Markus HS, Mathew CG, McLean WH, McManus R, Mossner R, Moutsianas L, Naluai AT, Nestle FO, Novelli G, Onoufriadis A, Palmer CN, Perricone C, Pirinen M, Plomin R, Potter SC, Pujol RM, Rautanen A, Riveira-Munoz E, Ryan AW, Salmhofer W, Samuelsson L, Sawcer SJ, Schalkwijk J, Smith CH, Stahle M, Su Z, Tazi-Ahnini R, Traupe H, Viswanathan AC, Warren RB, Weger W, Wolk K, Wood N, Worthington J, Young HS, Zeeuwen PL, Hayday A, Burden AD, Griffiths CE, Kere J, Reis A, McVean G, Evans DM, Brown MA, Barker JN, Peltonen L, Donnelly P, Trembath RC (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 42(11):985–990. doi:10.1038/ng.694

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Yumei-Wu for his assistance and he has given us detailed explanation of their research.

Conflict of interest

The data given are original data, have not been published before and are not being considered for publication elsewhere. The authors state no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Dermatology, Affiliated Hospital of Guangdong Medical College, No. 57, Remnin Avenue, Xiashan district, Zhanjiang, 524001, Guangdong, China

    Kun-Ju Zhu, Cheng-Yao Zhu, Ge Shi & Yi-Ming Fan

Authors
  1. Kun-Ju Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cheng-Yao Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ge Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi-Ming Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kun-Ju Zhu or Yi-Ming Fan.

Additional information

Kun-Ju Zhu and Cheng-Yao Zhu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, KJ., Zhu, CY., Shi, G. et al. Meta-analysis of IL12B polymorphisms (rs3212227, rs6887695) with psoriasis and psoriatic arthritis. Rheumatol Int 33, 1785–1790 (2013). https://doi.org/10.1007/s00296-012-2637-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-012-2637-4

Keywords

Search

Navigation