Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

IL12B and IL23R polymorphisms are associated with alopecia areata


Alopecia areata is an autoimmune disease in which activation of autoreactive T cells and inflammatory immune signals target the hair follicles autoantigens. Although cytokines are involved in regulating autoimmune inflammation, the specific involvement of these molecules in the pathogenesis of alopecia areata has been remained unsettled. Here, a possible influence of IL12B, IL17A, and IL23R variations on susceptibility to alopecia areata in Iranian patients was investigated. Genotyping of IL12B (rs3212227), IL17A (rs2275913), and IL23R (rs10889677) variants were performed by extracting genomic DNA from patients and controls. Gene expression was analyzed by real-time RT-PCR. The frequency of IL12B and IL23R gene polymorphisms is significantly higher in the patients than controls, while no significant difference was found for IL17A. Stratification of the patients with respect to age at disease onset indicated that CC genotype of IL12B (rs3212227) and AA genotype of IL23R (rs10889677) gene polymorphisms are significantly associated with late-onset alopecia areata disease. In contrast to IL17A and IL23R, IL12B gene expression levels elevated in patients to that of controls, but genotypes had no effect on levels of gene expression. Overall, our data confirmed that the IL12B and IL23R polymorphisms are associated with the risk to develop alopecia areata in our population.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Comparison of gene expression levels of IL12B, IL17A, and IL23R in patients with alopecia areata and control subjects.
Fig. 2: Stratification of the genotypes in patients based on gene expression.


  1. 1.

    Guo H, Cheng Y, Shapiro J, McElwee K. The role of lymphocytes in the development and treatment of alopecia areata. Expert Rev Clin Immunol. 2015;11:1335–51.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010;62:177–88. quiz 89–90.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol. 2015;8:397–403.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Biran R, Zlotogorski A, Ramot Y. The genetics of alopecia areata: new approaches, new findings, new treatments. J Dermatol Sci. 2015;78:11–20.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Teng MW, Bowman EP, McElwee JJ, Smyth MJ, Casanova JL, Cooper AM, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21:719–29.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Qian C, Jiang T, Zhang W, Ren C, Wang Q, Qin Q, et al. Increased IL-23 and IL-17 expression by peripheral blood cells of patients with primary biliary cirrhosis. Cytokine. 2013;64:172–80.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Fransen K, van Sommeren S, Westra HJ, Veenstra M, Lamberts LE, Modderman R, et al. Correlation of genetic risk and messenger RNA expression in a Th17/IL23 pathway analysis in inflammatory bowel disease. Inflamm Bowel Dis. 2014;20:777–82.

    PubMed  Article  Google Scholar 

  8. 8.

    Carroll JM, McElwee KJ, L EK, Byrne MC, Sundberg JP. Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans. J Investig Dermatol. 2002;119:392–402.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Subramanya RD, Coda AB, Sinha AA. Transcriptional profiling in alopecia areata defines immune and cell cycle control related genes within disease-specific signatures. Genomics. 2010;96:146–53.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Malik K, Guttman-Yassky E. Cytokine targeted therapeutics for alopecia areata: lessons from atopic dermatitis and other inflammatory skin diseases. J Investig Dermatol Symp Proc. 2018;19:S62–s4.

    PubMed  Article  Google Scholar 

  11. 11.

    Suarez-Farinas M, Ungar B, Noda S, Shroff A, Mansouri Y, Fuentes-Duculan J, et al. Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing. J Allergy Clin Immunol. 2015;136:1277–87.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Bain KA, McDonald E, Moffat F, Tutino M, Castelino M, Barton A, et al. Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease-associated psychological morbidity. Br J Dermatol. 2020;182:130–7.

    CAS  PubMed  Google Scholar 

  13. 13.

    Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet. 2007;80:273–90.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Safrany E, Szell M, Csongei V, Jaromi L, Sipeky C, Szabo T, et al. Polymorphisms of the IL23R gene are associated with psoriasis but not with immunoglobulin A nephropathy in a Hungarian population. Inflammation. 2011;34:603–8.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Zwiers A, Seegers D, Heijmans R, Koch A, Hampe J, Nikolaus S, et al. Definition of polymorphisms and haplotypes in the interleukin-12B gene: association with IL-12 production but not with Crohn’s disease. Genes Immun. 2004;5:675–7.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Xu WD, Xie QB, Zhao Y, Liu Y. Association of Interleukin-23 receptor gene polymorphisms with susceptibility to Crohn’s disease: a meta-analysis. Sci Rep. 2015;5:18584.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Orozco G, Gonzalez-Gay MA, Paco L, Lopez-Nevot MA, Guzman M, Pascual-Salcedo D, et al. Interleukin 12 (IL12B) and interleukin 12 receptor (IL12RB1) gene polymorphisms in rheumatoid arthritis. Hum Immunol. 2005;66:710–5.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Farago B, Magyari L, Safrany E, Csongei V, Jaromi L, Horvatovich K, et al. Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis. Ann Rheum Dis. 2008;67:248–50.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Sandip C, Tan L, Huang J, Li Q, Ni L, Cianflone K, et al. Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure. Medicine. 2016;95:e4105.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Stappers MH, Thys Y, Oosting M, Plantinga TS, Ioana M, Reimnitz P, et al. Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections. Eur J Clin Microbiol Infect Dis. 2014;33:2267–74.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Bogunia-Kubik K, Swierkot J, Malak A, Wysoczanska B, Nowak B, Bialowas K, et al. IL-17A, IL-17F and IL-23R gene polymorphisms in Polish patients with rheumatoid arthritis. Arch Immunol Ther Exp. 2015;63:215–21.

    CAS  Article  Google Scholar 

  22. 22.

    Hayashi R, Tahara T, Shiroeda H, Saito T, Nakamura M, Tsutsumi M, et al. Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility to ulcerative colitis. Clin Exp Med. 2013;13:239–44.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Yaghini N, Mahmoodi M, Hassanshahi G, Asadikaram G, Arababadi MK, Rezaeian M, et al. Genetic variation of IL-12B (+1188 region) is associated with its decreased circulating levels and susceptibility to Type 2 diabetes. Biomark Med. 2012;6:89–95.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Lew BL, Cho HR, Haw S, Kim HJ, Chung JH, Sim WY. Association between IL17A/IL17RA gene polymorphisms and susceptibility to alopecia areata in the Korean Population. Ann Dermatol. 2012;24:61–5.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Aytekin N, Akcali C, Pehlivan S, Kirtak N, Inaloz S. Investigation of interleukin-12, interleukin-17 and interleukin-23 receptor gene polymorphisms in alopecia areata. J Int Med Res. 2015;43:526–34.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Akatsu T, Nakamura M, Satoh M, Hiramori K. Increased mRNA expression of tumour necrosis factor-alpha and its converting enzyme in circulating leucocytes of patients with acute myocardial infarction. Clin Sci. 2003;105:39–44.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Ghaderian SM, Akbarzadeh Najar R, Tabatabaei Panah AS. Tumor necrosis factor-alpha: investigation of gene polymorphism and regulation of TACE-TNF-alpha system in patients with acute myocardial infarction. Mol Biol Rep. 2011;38:4971–7.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Urabe S, Isomoto H, Ishida T, Maeda K, Inamine T, Kondo S, et al. Genetic polymorphisms of IL-17F and TRAF3IP2 could be predictive factors of the long-term effect of infliximab against Crohn’s Disease. Biomed Res Int. 2015;2015:416838.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  30. 30.

    Conic RZ, Miller R, Piliang M, Bergfeld W, Atanaskova Mesinkovska N. Comorbidities in patients with alopecia areata. J Am Acad Dermatol. 2017;76:755–7.

    PubMed  Article  Google Scholar 

  31. 31.

    Blaumeiser B, van der Goot I, Fimmers R, Hanneken S, Ritzmann S, Seymons K, et al. Familial aggregation of alopecia areata. J Am Acad Dermatol. 2006;54:627–32.

    PubMed  Article  Google Scholar 

  32. 32.

    Moravvej H, Tabatabaei-Panah PS, Abgoon R, Khaksar L, Sokhandan M, Tarshaei S, et al. Genetic variant association of PTPN22, CTLA4, IL2RA, as well as HLA frequencies in susceptibility to alopecia areata. Immunol Investig. 2018;47:666–79.

    CAS  Google Scholar 

  33. 33.

    Moravvej H, Tabatabaei-Panah PS, Ebrahimi E, Esmaeili N, Ghaderian SMH, Ludwig RJ, et al. TNF-alpha -308G/A gene polymorphism in bullous pemphigoid and alopecia areata. Hum Antibodies 2018;26:201–7.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Tabatabaei-Panah PS, Moravvej H, Arian S, Fereidonpour I, Behravesh N, Atoon A, et al. Overlapping and distinct FAS/FASLG gene polymorphisms in alopecia areata in an Iranian population. Immunol Investig. 2020;49:2014–14.

    Google Scholar 

  35. 35.

    Rajabi F, Amoli MM, Robati RM, Almasi-Nasrabadi M, Jabalameli N, Moravvej H. The association between genetic variation in Wnt transcription factor TCF7L2 (TCF4) and alopecia areata. Immunol Investig. 2019;48:555–62.

    CAS  Article  Google Scholar 

  36. 36.

    Gilhar A, Shalaginov R, Assy B, Serafimovich S, Kalish RS. Alopecia areata is a T-lymphocyte mediated autoimmune disease: lesional human T-lymphocytes transfer alopecia areata to human skin grafts on SCID mice. J Investig Dermatol Symp Proc. 1999;4:207–10.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Wasserman D, Guzman-Sanchez DA, Scott K, McMichael A. Alopecia areata. Int J Dermatol. 2007;46:121–31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Tabarkiewicz J, Pogoda K, Karczmarczyk A, Pozarowski P, Giannopoulos K. The role of IL-17 and Th17 lymphocytes in autoimmune diseases. Arch Immunol Ther Exp. 2015;63:435–49.

    CAS  Article  Google Scholar 

  39. 39.

    Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715–25.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Zhou L, Yao F, Luan H, Wang Y, Dong X, Zhou W, et al. Functional polymorphisms in the interleukin-12 gene contribute to cancer risk: evidence from a meta-analysis of 18 case-control studies. Gene. 2012;510:71–7.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Peng LL, Wang Y, Zhu FL, Xu WD, Ji XL, Ni J. IL-23R mutation is associated with ulcerative colitis: a systemic review and meta-analysis. Oncotarget. 2017;8:4849–63.

    PubMed  Article  Google Scholar 

  42. 42.

    Seegers D, Zwiers A, Strober W, Pena AS, Bouma G. A TaqI polymorphism in the 3’UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun. 2002;3:419–23.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Yilmaz V, Yentur SP, Saruhan-Direskeneli G. IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine. 2005;30:188–94.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    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;27:218–21.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Espinoza JL, Takami A, Nakata K, Onizuka M, Kawase T, Akiyama H, et al. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation. PLoS ONE. 2011;6:e26229.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Maalmi H, Beraies A, Charad R, Ammar J, Hamzaoui K, Hamzaoui A. IL-17A and IL-17F genes variants and susceptibility to childhood asthma in Tunisia. J Asthma. 2014;51:348–54.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Chen J, Deng Y, Zhao J, Luo Z, Peng W, Yang J, et al. The polymorphism of IL-17 G-152A was associated with childhood asthma and bacterial colonization of the hypopharynx in bronchiolitis. J Clin Immunol. 2010;30:539–45.

    CAS  PubMed  Article  Google Scholar 

Download references


We would like to thank the Medical and Nursing staff of the Skin Research Center, Shohada Tajrish and Loghman Hakim hospitals at Tehran, Iran for helpful collaboration.

Author information



Corresponding author

Correspondence to Reza Akbarzadeh.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.


The study protocol was considered and approved by the local ethics committee (Human Research Ethics Committee of Skin Research Center, Shahid Beheshti University of Medical Sciences). The investigation conforms to the principles outlined in the 1964 Declaration of Helsinki, revised in 2000.

Informed consent

Informed patient consent was obtained from all individuals.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tabatabaei-Panah, PS., Moravvej, H., Delpasand, S. et al. IL12B and IL23R polymorphisms are associated with alopecia areata. Genes Immun 21, 203–210 (2020).

Download citation

Further reading


Quick links