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Association of IL-23R and IL-10 variations with Behçet disease: a genetic analysis study

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Abstract

Behçet disease (BD) is an autoimmune and autoinflammatory disease mainly affecting the Silk Road countries. The interindividual severity of BD depends on differences in the polymorphic profiles of the patients. One of the most prominent markers, HLA-B51 positivity, is also observed in 40–60% of patients with BD on the Silk Road. Inflammatory markers such as interleukin 10 (IL-10) and interleukin 23 receptor (IL-23R) are also widely associated with BD etiology. The polymorphisms on these genes may change the susceptibility to BD. In this case-control study, we assessed the associations of IL-10 rs3024498 and IL-23R rs10889677 single-nucleotide polymorphisms (SNPs) with BD susceptibility, if any. Two hundred eighty HLA-B51-positive patients with BD and 300 healthy controls were genotyped for these SNPs using RFLP-PCR. The chi-square test was used for genotyping. We found that IL-23R rs10889677 CC and IL-10 rs3024498 CT genotype frequencies were higher in the BD group than in the control group (p < 0.0001 and p = 0.0293, respectively). The recessive model (AA + CC vs. AC) and combined genotype (AC + CT) results were also statistically significant (p < 0.0001 and p = 0.0364, respectively). We conclude that IL-23R rs10889677 and IL-10 rs3024498 SNPs may be associated with the susceptibility to BD.

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References

  1. Takeuchi M, Kastner DL, Remmers EF. The immunogenetics of Behçet's disease: a comprehensive review. J Autoimmun. 2015;64:137–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sakane T, Takeno M, Suzuki N, Inaba G. Behçet’s disease. New Engl J Med. 1999;341(17):1284–91.

    Article  CAS  PubMed  Google Scholar 

  3. Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet's Disease. Lancet. 1990;335(8697):1078–80.

    Google Scholar 

  4. Alipour S, Nouri M, Sakhinia E, Samadi N, Roshanravan N, Ghavami A, et al. Epigenetic alterations in chronic disease focusing on Behçet’s disease: review. Biomed Pharmacother. 2017;91:526–33. https://doi.org/10.1016/j.biopha.2017.04.106.

    Article  CAS  PubMed  Google Scholar 

  5. Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci. Nat Genet. 2010;42(8):703–6. https://doi.org/10.1038/ng.624.

    Article  CAS  PubMed  Google Scholar 

  6. Wallace G. Novel genetic analysis in Behcet’s disease. Arthritis Res Ther. 2009;11:123.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet’s disease. Nat Genet. 2010;42:698–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ilhan B, Can M, Alibaz-Oner F, Yilmaz-Oner S, Polat-Korkmaz O, Ozen G, et al. Fatigue in patients with Behçet’s syndrome: relationship with quality of life, depression, anxiety, disability and disease activity. Int J Rheum Dis. 2018;21(12):2139–45. https://doi.org/10.1111/1756-185X.12839.

    Article  CAS  PubMed  Google Scholar 

  9. Greco A, De Virgilio A, Ralli M, Ciofalo A, Mancini P, Attanasio G, et al. Behçet’s disease: new insights into pathophysiology, clinical features and treatment options. Autoimmun Rev. 2018;17(6):567–75. https://doi.org/10.1016/j.autrev.2017.12.006.

    Article  CAS  PubMed  Google Scholar 

  10. Khaib Dit Naib O, Aribi M, Idder A, Chiali A, Sairi H, Touitou I, et al. Association analysis of IL10, TNF-α, and IL23R-IL12RB2 SNPs with Behçet’s disease risk in Western Algeria. Front Immunol. 2013;21(4):342. https://doi.org/10.3389/fimmu.2013.00342.

    Article  Google Scholar 

  11. Yazici H, Fresko I, Yurdakul S. Behçet’s syndrome: disease manifestations, management, and advances in treatment. Nat Clin Pract Rheumatol. 2007;3(3):148–55.

    Article  PubMed  Google Scholar 

  12. Vandenbroeck K. Cytokine gene polymorphisms and human autoimmune disease in the era of genome-wide association studies. J Interferon Cytokine Res. 2012;32(4):139–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vandenbroeck K, editor. Cytokine gene polymorphisms in multifactorial conditions. 1st ed. CRC Press; 2006. https://doi.org/10.1201/9781420005325.

    Book  Google Scholar 

  14. Shahriyari E, Vahedi L, Roshanipour N, Jafarabadi MA, Khamaneh A, Laleh MG. Exploring the association of IL10 polymorphisms in Behcet’s disease: a systematic review and meta-analysis. J Inflamm (Lond). 2019;23(16):26. https://doi.org/10.1186/s12950-019-0230-2.

    Article  CAS  Google Scholar 

  15. Afkari B, Babaloo Z, Dolati S, Khabazi A, Jadidi-Niaragh F, Talei M, et al. Molecular analysis of interleukin 10 gene polymorphisms in patients with Behçet’s disease. Immunol Lett. 2018;194:56–61. https://doi.org/10.1016/j.imlet.2017.12.008.

    Article  CAS  PubMed  Google Scholar 

  16. Yu H, Zheng M, Zhang L, Li H, Zhu Y, Cheng L, et al. Identification of susceptibility SNPs in IL10 and IL23R-IL12RB2 for Behçet’s disease in Han Chinese. J Allergy Clin Immunol. 2017;139(2):621–7. https://doi.org/10.1016/j.jaci.2016.05.024.

    Article  CAS  PubMed  Google Scholar 

  17. Braga M, Lara-Armi FF, Neves JSF, Rocha-Loures MA, Terron-Monich MS, Bahls-Pinto LD, et al. Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL10, IL-17A, and IL17F serum levels in ankylosing spondylitis. Front Immunol. 2021;5(12):653611. https://doi.org/10.3389/fimmu.2021.653611.

    Article  CAS  Google Scholar 

  18. Touzot M, Cacoub P, Bodaghi B, Soumelis V, Saadoun D. IFN-α induces IL-10 production and tilt the balance between Th1 and Th17 in Behçet disease. Autoimmun Rev. 2015;14(5):370–5. https://doi.org/10.1016/j.autrev.2014.12.009.

    Article  CAS  PubMed  Google Scholar 

  19. Emmi G, Silvestri E, Bella CD, Grassi A, Benagiano M, Cianchi F, et al. Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease. Medicine (Baltimore). 2016;95(49):e5516. https://doi.org/10.1097/MD.0000000000005516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. International Team for the Revision of the International Criteria for Behçet's Disease [ITR-ICBD]. The International Criteria for Behçet's Disease [ICBD]: a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol. 2014;28(3):338–47.

    Article  Google Scholar 

  21. Morton LT, Situnayake D, Wallace GR. Genetics of Behçet’s disease. Curr Opin Rheumatol. 2016;28(1):39–44.

    Article  CAS  PubMed  Google Scholar 

  22. Zhou S, Ruan Y, Yu H, Chen Y, Yao Y, Ma Y, et al. Functional IL23R rs10889677 genetic polymorphism and risk of multiple solid tumors: a meta-analysis. PLoS One. 2013;8(11):e80627. https://doi.org/10.1371/journal.pone.0080627.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zwiers A, Kraal L, van de Pouw Kraan TC, Wurdinger T, Bouma G, Kraal G. Cutting edge: a variant of the IL-23R gene associated with inflammatory bowel disease induces loss of microRNA regulation and enhanced protein production. J Immunol. 2012;188(4):1573–7. https://doi.org/10.4049/jimmunol.1101494.

    Article  CAS  PubMed  Google Scholar 

  24. Yalçin B, Atakan N, Dogan S. Association of interleukin 23 receptor gene polymorphism with Behçet disease. Clin Exp Dermatol. 2014;39(8):881–7. https://doi.org/10.1111/ced.12400.

    Article  PubMed  Google Scholar 

  25. Szabo M, Safrany E, Pazar B, Melegh BI, Kisfali P, Poor G, et al. Marked diversity of IL23R gene haplotype variants in rheumatoid arthritis comparing with Crohn’s disease and ankylosing spondylitis. Mol Biol Rep. 2013;40(1):359–63. https://doi.org/10.1007/s11033-012-2068-z.

    Article  CAS  PubMed  Google Scholar 

  26. 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(6):603–8. https://doi.org/10.1007/s10753-010-9268-2.

    Article  CAS  PubMed  Google Scholar 

  27. Orozco G, Rueda B, Robledo G, García A, Martín J. Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort. Hum Immunol. 2007;68(8):681–4.

    Article  CAS  PubMed  Google Scholar 

  28. Huang J, Yang Y, Zhou F, Liang Z, Kang M, Kuang Y, et al. Meta-analysis of the IL23R and IL12B polymorphisms in multiple sclerosis. Int J Neurosci. 2016;126(3):205–12. https://doi.org/10.3109/00207454.2015.1007508.

    Article  CAS  PubMed  Google Scholar 

  29. Poomarimuthu M, Elango S, Solomon PR, Soundrapandian S, Mariakuttikan J. Association of IL17 and IL23R gene polymorphisms with rheumatic heart disease in South Indian population. Immunol Invest. 2018;47(7):754–64.

    Article  CAS  PubMed  Google Scholar 

  30. Omrane I, Baroudi O, Bougatef K, Mezlini A, Abidi A, Medimegh I, et al. Significant association between IL23R and IL17F polymorphisms and clinical features of colorectal cancer. Immunol Lett. 2014;158(1-2):189–94. https://doi.org/10.1016/j.imlet.2014.01.002.

    Article  CAS  PubMed  Google Scholar 

  31. Nemati K, Golmoghaddam H, Hosseini SV, Ghaderi A, Doroudchi M. Interleukin-17FT7488 allele is associated with a decreased risk of colorectal cancer and tumor progression. Gene. 2015;561(1):88–94.

    Article  CAS  PubMed  Google Scholar 

  32. Salim PH, Xavier RM. Influência dos polimorfismos genéticos [IL10/CXCL8/CXCR2/ NFκB] na susceptibilidade das doenças reumatológicas autoimunes Influence of genetic polymorphisms IL10/CXCL8/CXCR2/NFκB on the susceptibility of autoimmune rheumatic diseases. Rev Bras Reumatol. 2014;54(4):301–10.

    Article  PubMed  Google Scholar 

  33. Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. New insights into the pathogenesis of Behçet’s disease. Autoimmun Rev. 2012;11(10):687–98.

    Article  CAS  PubMed  Google Scholar 

  34. Tsilidis KK, Helzlsouer KJ, Smith MW, Grinberg V, Hoffman-Bolton J, Clipp SL, et al. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer. Cancer Causes Control. 2009;20(9):1739–51. https://doi.org/10.1007/s10552-009-9427-7.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sathyan S, Barzilai N, Atzmon G, Milman S, Ayers E, Verghese J, et al. Association of anti-inflammatory cytokine IL10 polymorphisms with motoric cognitive risk syndrome in an Ashkenazi Jewish population. Neurobiol Aging. 2017;58:238.e1–8.

    Article  CAS  PubMed  Google Scholar 

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GY designed and supervised the study; TSa provided the study samples; SS, SBY, and EA performed the experiments; GY, TSo, and TSa performed the data analysis and wrote the paper. All the authors have accepted their responsibility for the entire content of this manuscript and have approved its submission.

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Correspondence to Guven Yenmis.

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All authors stated that the protocol for the research project had been approved by the Institutional Ethical Committee of Biruni University (Decision no:2021/55-16).

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Yenmis, G., Sabancelebi, S., Atak, E. et al. Association of IL-23R and IL-10 variations with Behçet disease: a genetic analysis study. Immunol Res 72, 293–298 (2024). https://doi.org/10.1007/s12026-023-09433-w

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