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.
Similar content being viewed by others
References
Takeuchi M, Kastner DL, Remmers EF. The immunogenetics of Behçet's disease: a comprehensive review. J Autoimmun. 2015;64:137–48.
Sakane T, Takeno M, Suzuki N, Inaba G. Behçet’s disease. New Engl J Med. 1999;341(17):1284–91.
Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet's Disease. Lancet. 1990;335(8697):1078–80.
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.
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.
Wallace G. Novel genetic analysis in Behcet’s disease. Arthritis Res Ther. 2009;11:123.
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.
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.
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.
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.
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.
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.
Vandenbroeck K, editor. Cytokine gene polymorphisms in multifactorial conditions. 1st ed. CRC Press; 2006. https://doi.org/10.1201/9781420005325.
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.
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.
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.
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.
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.
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.
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.
Morton LT, Situnayake D, Wallace GR. Genetics of Behçet’s disease. Curr Opin Rheumatol. 2016;28(1):39–44.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Contributions
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.
Corresponding author
Ethics declarations
Ethics approval
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).
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12026-023-09433-w