Skip to main content

Advertisement

SpringerLink
Log in

CXCL9 and CXCL10 gene polymorphisms in patients with rheumatoid arthritis

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

Abstract

Chemokines (CXCL) and their receptors play important roles in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine the associations between polymorphisms in the CXCL9 (rs3733236 G>A) and CXCL10 (rs8878 A>G) genes and RA. We examined 422 RA patients and 338 subjects as a control group. Single nucleotide polymorphisms (SNPs) in the CXCL9 (rs3733236 G>A) and CXCL10 (rs8878 A>G) genes were genotyped using TaqMan genotyping assays from Life Technologies Genomic. There were no significant differences in distribution of CXCL9 genotypes and alleles between RA patients and control group. Among RA patients, the increased frequency of CXCL10 (rs8878) G allele carriers was detected AG+GG vs AA (p = 0.034; OR 1.49, 95 % CI 1.03–2.13). There were no significant associations of CXCL9 genotypes with age of disease diagnosis rheumatoid factor, erosive disease, and extra-articular manifestations. In case of CXCL10 genotypes, there was the increased frequency of extra-articular manifestations in GG genotype carriers GG vs AA+AG (p = 0.027; OR 1.82, 95 % CI 1.09–3.03). In the multivariate regression analysis, the CXCL10 GG genotype was the independent factor associated with increased probability of extra-articular manifestations development (p = 0.034; OR 1.75, 95 % CI 1.04–3.03). The results of this study suggest the association between CXCL10 gene polymorphism and rheumatoid arthritis.

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

Similar content being viewed by others

References

  1. Ruth JH, Rottman JB, Katschke KJ Jr et al (2001) Selective lymphocyte chemokine receptor expression in the rheumatoid joint. Arthritis Rheum 44:2750–2760

    Article  CAS  PubMed  Google Scholar 

  2. Taub DD, Lloyd AR, Conlon K et al (1993) Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med 177:1809–1814

    Article  CAS  PubMed  Google Scholar 

  3. Jinquan T, Jing C, Jacobi HH et al (2000) CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma. J Immunol 165:1548–1556

    Article  CAS  PubMed  Google Scholar 

  4. Yin Z, Siegert S, Neure L et al (1999) The elevated ratio of interferon gamma-/interleukin-4-positive T cells found in synovial fluid and synovial membrane of rheumatoid arthritis patients can be changed by interleukin-4 but not by interleukin-10 or transforming growth factor beta. Rheumatology (Oxford) 38:1058–1067

    Article  CAS  Google Scholar 

  5. Canete JD, Martinez SE, Farres J et al (2000) Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies. Ann Rheum Dis 59:263–268

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242

    Article  CAS  PubMed  Google Scholar 

  7. Garcia-Lopez MA, Sanchez-Madrid F, Rodriguez-Frade JM et al (2001) CXCR3 chemokine receptor distribution in normal and inflamed tissues: expression on activated lymphocytes, endothelial cells, and dendritic cells. Lab Investig 81:409–418

    Article  CAS  PubMed  Google Scholar 

  8. Hanaoka R, Kasama T, Muramatsu M et al (2003) A novel mechanism for the regulation of IFN-gamma inducible protein-10 expression in rheumatoid arthritis. Arthritis Res Ther 5:R74–R81

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Patel DD, Zachariah JP, Whichard LP (2001) CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immunol 98:39–45

    Article  CAS  PubMed  Google Scholar 

  10. Lee EY, Seo MR, Juhn Y-S et al (2011) Potential role and mechanism of IFN-gamma inducible protein-10 on receptor activator of nuclear factor kappa-B ligand (RANKL) expression in rheumatoid arthritis. Arthritis Res Ther 13:R104

    Article  PubMed Central  PubMed  Google Scholar 

  11. Klich I, Fendler W, Wyka K, Młynarski W (2011) Effect of the IP10 (CXCL10) and HLA genotype on the risk of type 1 diabetes in children. Pediatr Endocrinol Diabetes Metab 17:10–13

    CAS  PubMed  Google Scholar 

  12. Nogueira LG, Santos RH, Ianni BM et al (2012) Myocardial chemokine expression and intensity of myocarditis in Chagas cardiomyopathy are controlled by polymorphisms in CXCL9 and CXCL10. PLoS Negl Trop Dis 6:e1867

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Lacher M, Kappler R, Berkholz S, Baurecht H, von Schweinitz D, Koletzko S (2007) Association of a CXCL9 polymorphism with pediatric Crohn’s disease. Biochem Biophys Res Commun 363:701–707

    Article  CAS  PubMed  Google Scholar 

  14. Brück P, Bartsch W, Penna-Martinez M et al (2009) Polymorphisms of CXCR3-binding chemokines in type 1 diabetes. Hum Immunol 70:552–555

    Article  PubMed  Google Scholar 

  15. Venturelli E, Galimberti D, Fenoglio C et al (2006) Candidate gene analysis of IP-10 gene in patients with Alzheimer’s disease. Neurosci Lett 404:217–221

    Article  CAS  PubMed  Google Scholar 

  16. Galimberti D, Scalabrini D, Fenoglio C et al (2007) CXCL10 haplotypes and multiple sclerosis: association and correlation with clinical course. Eur J Neurol 14:162–167

    Article  CAS  PubMed  Google Scholar 

  17. Aletaha D, Neogi T, Silman AJ et al (2010) Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–25681

    Article  PubMed  Google Scholar 

  18. Dimberg J, Skarstedt M, Löfgren S, Zar N, Matussek A (2014) Protein expression and gene polymorphism of CXCL10 in patients with colorectal cancer. Biomed Rep 2:340–343

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Kuan WP, Tam LS, Wong CK, Ko FW, Li T, Zhu T, Li EK (2010) CXCL 9 and CXCL 10 as Sensitive markers of disease activity in patients with rheumatoid arthritis. J Rheumatol 37:257–264

    Article  CAS  PubMed  Google Scholar 

  20. Ruschpler P, Lorenz P, Eichler W et al (2003) High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis. Arthritis Res Ther 5:R241–R252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Yoshida S, Arakawa F, Higuchi F et al (2012) Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5. Scand J Rheumatol 41:170–179

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Ogawa N, Ping L, Zhenjun L, Takada Y, Sugai S (2002) Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren’s syndrome. Arthritis Rheum 46:2730–2741

    Article  CAS  PubMed  Google Scholar 

  23. Yellin M, Paliienko I, Balanescu A et al (2012) A Phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 64:1730–1739

    Article  CAS  PubMed  Google Scholar 

  24. Kwak HB, Ha H, Kim HN et al (2008) Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsible for bone erosive experimental arthritis. Arthritis Rheum 58:1332–1342

    Article  CAS  PubMed  Google Scholar 

  25. Kwak HB, Lee SW, Jin HM et al (2005) Monokine induced by interferon-gamma is induced by receptor activator of nuclear factor kappa B ligand and is involved in osteoclast adhesion and migration. Blood 105:2963–2969

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Departament of Orthopaedics, Traumatology and Orthopaedic Oncology, Pomeranian Medical University, Szczecin, Poland

    Daniel Kotrych

  2. Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland

    Violetta Dziedziejko & Krzysztof Safranow

  3. Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland

    Marek Drozdzik

  4. Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland

    Andrzej Pawlik

Authors
  1. Daniel Kotrych
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Violetta Dziedziejko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Krzysztof Safranow
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marek Drozdzik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrzej Pawlik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrzej Pawlik.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kotrych, D., Dziedziejko, V., Safranow, K. et al. CXCL9 and CXCL10 gene polymorphisms in patients with rheumatoid arthritis. Rheumatol Int 35, 1319–1323 (2015). https://doi.org/10.1007/s00296-015-3234-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-015-3234-0

Keywords

Search

Navigation