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A functional microRNA binding site variant in IL-23R gene in systemic lupus erythematosus and rheumatoid arthritis: is there any correlation?

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Abstract

Background

IL-23 receptor (IL-23R) dysregulation has been shown to have critical roles in pathogenesis of different autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) via suppression of regulatory T cells (Tregs) as well as differentiation, expansion, and survival of T helper 17 (Th17) cells, followed by upregulation of interleukin 17 (IL-17). Here, we assessed the association of a functional microRNAs (miRNAs)-related single nucleotide polymorphism (miR-SNPs: rs10889677) in IL-23R, which was correlated with its overexpression and increased risk for SLE and RA in the Iranian population.

Methods

Genotype and allele distribution of rs10889677 variant were investigated in 105 RA patients, 100 SLE cases and 105 healthy controls via polymerase chain reaction– restriction fragment length polymorphism (PCR–RFLP) method.

Results

Our findings suggested that AA genotype, but not AC genotype, was associated with increased risk of RA (AA vs. CC; OR: 3.27; 95%CI [1.467–7.551]). The allele A was more frequent in RA group compared to controls (A allele vs. C allele; OR: 1.92; 95%CI [1.282–2.894]). This common variant was not significantly correlated with SLE risk in our population (P > 0.05). However, stratification analysis indicated that RA patients with AA genotype show higher serum concentration levels of C-reactive protein (CRP) (P: 0.008). No obvious correlation was noticed between different genotypes in SLE cases, except for a slight difference in terms of oral ulcer manifestation incidence (P: 0.038).

Conclusion

This study suggests a significant relationship between rs10889677 variant in IL-23R with increased risk of RA and some clinical features in RA and SLE patients.

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References

  1. Chen Z et al (2007) Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 56(9):2936–2946

    Article  CAS  Google Scholar 

  2. Boniface K et al (2008) From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. Immunol Rev 226:132–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kuwabara T et al (2017) The Role of IL-17 and Related Cytokines in Inflammatory Autoimmune Diseases. Mediat Inflamm 2017:3908061–3908061

    Article  Google Scholar 

  4. Tabarkiewicz J et al (2015) The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases. Arch Immunol Ther Exp 63(6):435–449

    Article  CAS  Google Scholar 

  5. El-Leithy S et al (2020) Cutaneous immunohistochemical expression of interleukin-23 receptor (IL-23R) in psoriasis and psoriatic arthritis patients: relation to musculoskeletal ultrasound findings. Egypt Rheumatologist 42(4):313–318

    Article  Google Scholar 

  6. Raychaudhuri SK et al (2020) Functional significance of MAIT cells in psoriatic arthritis. Cytokine 125:154855

    Article  CAS  PubMed  Google Scholar 

  7. Wang X et al (2010) Single-nucleotide polymorphisms and expression of IL23R in Chinese ankylosing spondylitis patients. Rheumatol Int 30(7):955–959

    Article  CAS  PubMed  Google Scholar 

  8. Peng H et al (2015) Decreased expression of microRNA-125a-3p upregulates interleukin-23 receptor in patients with Hashimoto’s thyroiditis. Immunol Res 62(2):129–136

    Article  CAS  PubMed  Google Scholar 

  9. Song L et al (2013) High intestinal and systemic levels of interleukin-23/T-helper 17 pathway in Chinese patients with inflammatory bowel disease. Mediators of inflammation, 2013

  10. Yang J et al (2009) Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthr Rhuem 60(5):1472–1483

    Article  Google Scholar 

  11. Puwipirom H et al (2010) Increased interleukin-23 receptor + T cells in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Arthritis Res Therapy 12(6):R215

    Article  CAS  Google Scholar 

  12. Shen H, Goodall JC, Hill Gaston J (2009) Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 60(6):1647–1656

    Article  CAS  Google Scholar 

  13. Gao J et al (2018) MiRNA-126 expression inhibits IL-23R mediated TNF-α or IFN-γ production in fibroblast-like synoviocytes in a mice model of collagen-induced rheumatoid arthritis. Apoptosis 23(11):607–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rose J (2022) Autoimmune connective tissue diseases: systemic lupus erythematosus and rheumatoid arthritis. Emerg Med Clin 40(1):179–191

    Article  Google Scholar 

  15. Lim J, Kim K (2019) Genetic variants differentially associated with rheumatoid arthritis and systemic lupus erythematosus reveal the disease-specific biology. Sci Rep 9(1):2739–2739

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lu H et al (2021) Detection of Genetic Overlap Between Rheumatoid Arthritis and Systemic Lupus Erythematosus Using GWAS Summary Statistics. Front Genet 12:656545–656545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Karimzadeh MR et al (2020) MicroRNA binding site polymorphism in inflammatory genes associated with colorectal cancer: literature review and bioinformatics analysis. Cancer Gene Ther 27(10):739–753

    Article  CAS  PubMed  Google Scholar 

  18. Hassani M et al (2021) Investigation of rs531564 polymorphism in the primary microRNA-124 gene in patients with systemic lupus erythematosus and rheumatoid arthritis: association with disease susceptibility and clinical characteristics.Iranian Journal of Allergy, Asthma and Immunology, : p.1–11

  19. Mishra PJ et al (2008) MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell: Introducing microRNA pharmacogenomics. Cell Cycle 7(7):853–858

    Article  CAS  PubMed  Google Scholar 

  20. Ehtesham N et al (2021) Three functional variants in the NLRP3 gene are associated with susceptibility and clinical characteristics of systemic lupus erythematosus. Lupus 30(8):1273–1282

    Article  CAS  PubMed  Google Scholar 

  21. Zwiers A et al (2012) 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 188(4):1573–1577

    Article  CAS  PubMed  Google Scholar 

  22. Zheng J et al (2012) Functional genetic variations in the IL-23 receptor gene are associated with risk of breast, lung and nasopharyngeal cancer in Chinese populations. Carcinogenesis 33(12):2409–2416

    Article  CAS  PubMed  Google Scholar 

  23. Mosallaei M et al (2019) Single nucleotide polymorphism rs10889677 in miRNAs Let-7e and Let-7f binding site of IL23R gene is a strong colorectal cancer determinant: Report and meta-analysis. Cancer Genet 239:46–53

    Article  PubMed  Google Scholar 

  24. Liu X-H et al (2015) Association of IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) with cancer risk: a PRISMA-compliant meta-analysis. Medicine, 94(52)

  25. Tabatabaei-Panah P-S et al (2020) IL12B and IL23R polymorphisms are associated with alopecia areata. Genes & Immunity 21(3):203–210

    Article  CAS  Google Scholar 

  26. Faragó B et al (2008) Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis. Ann Rheum Dis 67(2):248–250

    Article  PubMed  Google Scholar 

  27. Han R et al (2018) Interleukin-23 receptor polymorphism (rs10889677 A/C) in ankylosing spondylitis: Meta-analysis in Caucasian and Asian populations. Clin Chim Acta 477:53–59

    Article  CAS  PubMed  Google Scholar 

  28. Liu C-J et al (2021) miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets. Nucleic Acids Res 49(D1):D1276–D1281

    Article  CAS  PubMed  Google Scholar 

  29. Bruno AE et al (2012) miRdSNP: a database of disease-associated SNPs and microRNA target sites on 3’UTRs of human genes. BMC Genomics 13(1):1–7

    Article  Google Scholar 

  30. Aringer M et al (2019) 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis & rheumatology 71(9):1400–1412

    Article  Google Scholar 

  31. Zhou S et al (2013) Functional IL-23R rs10889677 genetic polymorphism and risk of multiple solid tumors: a meta-analysis. PLoS ONE 8(11):e80627

    Article  PubMed  PubMed Central  Google Scholar 

  32. Dessie G et al (2021) Evaluation of C-Reactive Protein and Associated Factors Among Patients Suffering from Rheumatoid Arthritis at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Open Access Rheumatology: Research and Reviews, 13: p.247

  33. Zhu Y et al (2020) Genetic association between IL23R rs11209026 and rs10889677 polymorphisms and risk of Crohn’s disease and ulcerative colitis: Evidence from 41 studies. Inflamm Res 69(1):87–103

    Article  CAS  PubMed  Google Scholar 

  34. Emami S et al (2016) IL 23R gene polymorphism with juvenile idiopathic arthritis and its association with serum IL-17A. Int J Rheum Dis 19(11):1189–1196

    Article  CAS  PubMed  Google Scholar 

  35. Zhang T et al (2022) Associations between IL-23R gene polymorphism (rs10889677 A/C) and ankylosing spondylitis and rheumatoid arthritis susceptibility: A meta-analysis with trial sequential analysis. Autoimmunity, : p.1–10

  36. Safrany E et al (2009) Variants of the IL23R gene are associated with ankylosing spondylitis but not with Sjögren syndrome in Hungarian population samples. Scand J Immunol 70(1):68–74

    Article  CAS  PubMed  Google Scholar 

  37. Einarsdottir E et al (2009) IL23R in the Swedish, Finnish, Hungarian and Italian populations: association with IBD and psoriasis, and linkage to celiac disease. BMC Med Genet 10(1):1–10

    Article  Google Scholar 

  38. Elesawy F et al (2021) Evaluation of Interleukin-23 Receptor Gene Polymorphism in Vitiligo Patients. Benha J Appl Sci 6(2):61–64

    Article  Google Scholar 

  39. Poomarimuthu M et al (2018) Association of IL17 and IL23R gene polymorphisms with rheumatic heart disease in South Indian population. Immunol Investig 47(7):754–764

    Article  CAS  Google Scholar 

  40. Orozco G et al (2007) Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort. Hum Immunol 68(8):681–684

    Article  CAS  PubMed  Google Scholar 

  41. Hamdy G et al (2015) Association of interleukin-23 receptor (IL-23R) gene polymorphisms (rs11209026, rs2201841 and rs10889677) with Egyptian rheumatoid arthritis patients. Egypt Rheumatologist 37(4):159–163

    Article  Google Scholar 

  42. Chen G-M et al (2013) Lack of association between IL-23R gene polymorphisms and systemic lupus erythematosus in a Chinese population. Inflamm Res 62(8):791–795

    Article  CAS  PubMed  Google Scholar 

  43. Li Y et al (2010) The association between interleukin-23 receptor gene polymorphisms and systemic lupus erythematosus. DNA Cell Biol 29(2):79–82

    Article  PubMed  Google Scholar 

  44. Safrany E et al (2010) Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients. Inflamm Res 59(2):159–164

    Article  CAS  PubMed  Google Scholar 

  45. Azadeh N et al (2021) Genetic Association of Interkeukin-21 and Interleukin-23 Receptor Polymorphisms With Systemic Lupus Erythematosus in Iranian Population.

  46. Soysal E et al (2021) IL-23R gene polymorphisms in rheumatoid arthritis. Rheumatology International, : p.1–8

  47. Paradowska-Gorycka A et al (2018) Lack of association between rheumatoid arthritis and genetic variants rs10889677, rs11209026 and rs2201841 of IL-23R gene. Med Clin 151(5):191–195

    Article  Google Scholar 

  48. Sanchez E et al (2007) Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus. Tissue Antigens 70(3):233–237

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all patients who participated in this study. Also, we would like to appreciate the financial support provided by Semnan University of Medical Science.

Author information

Authors and Affiliations

  1. Rheumatology and Internal Medicine, Rheumatology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Samira Alesaeidi

  2. Department of Medical Genetics, Semnan University of Medical Sciences, Semnan, Iran

    Saeed Esmaeili Dizghandi, Tahereh Ghorashi & Mohsen Soosanabadi

  3. Department of Internal Medicine, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Goli Siri

  4. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Meysam Mosallaei

  5. Student Research Committee, Faculty of Statistics, University of Social Welfare and Rehabilitation Science, Tehran, Iran

    Meysam Mosallaei & Taiebe Kenarangi

  6. Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Mohsen Soosanabadi

  7. Department of Medical Genetics and Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Mohsen Soosanabadi

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  1. Samira Alesaeidi
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Correspondence to Mohsen Soosanabadi.

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Alesaeidi, S., Dizghandi, S.E., Siri, G. et al. A functional microRNA binding site variant in IL-23R gene in systemic lupus erythematosus and rheumatoid arthritis: is there any correlation?. Mol Biol Rep 49, 11821–11828 (2022). https://doi.org/10.1007/s11033-022-07922-z

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