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01-05-2009 | Original Article

Lack of association between interleukin 23 receptor gene polymorphisms and rheumatoid arthritis susceptibility

Authors: Jeong Ha Park, Yun Jung Kim, Byung Lae Park, Joon Seol Bae, Hyoung Doo Shin, Sang-Cheol Bae

Published in: Rheumatology International | Issue 7/2009

Abstract

The recent discovery of interleukin 23 (IL-23), its receptor, and the underlying signal transduction pathway has improved our understanding of cellular immunity. Several studies suggest that IL-23 is an essential promoter of chronic joint inflammation. In this report, we assess the possible association of interleukin 23 receptor (IL23R) polymorphisms and haplotypes with rheumatoid arthritis (RA). The study was conducted on 1,204 RA patients and 979 healthy controls. Seven polymorphisms were selected from previous IBD reports. The seven SNPs (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032 and rs1495965) were genotyped using the TaqMan assay. Comparison of RA and control subjects revealed no statistically significant differences in the distribution of the IL23R genotypes and haplotypes. Our results clearly indicate that IL23R gene polymorphisms do not play a significant role in susceptibility to RA in the Korean population. Accordingly, we conclude that IL23R gene polymorphisms cannot be applied as an effective genetic marker for RA susceptibility.

Weyand CM, Goronzy JJ (2000) Association of MHC and rheumatoid arthritis. HLA polymorphisms in phenotypic variants of rheumatoid arthritis. Arthritis Res 2:212–216. doi:10.1186/ar90 PubMedCrossRef

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463. doi:10.1126/science.1135245 PubMedCrossRef

Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910–1914. doi:10.1074/jbc.M207577200 PubMedCrossRef

Langrish CL, McKenzie BS, Wilson NJ, Malefyt R, Kastelein RA, Cua DJ (2004) IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev 202:96–105. doi:10.1111/j.0105-2896.2004.00214.x PubMedCrossRef

Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ (2003) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198:1951–1957. doi:10.1084/jem.20030896 PubMedCrossRef

Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748. doi:10.1038/nature01355 PubMedCrossRef

Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240. doi:10.1084/jem.20041257 PubMedCrossRef

Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324. doi:10.1002/art.1780310302 PubMedCrossRef

Oliver J, Rueda B, Lopez-Nevot MA, Gomez-Garcia M, Martin J (2007) Replication of an association between IL23R gene polymorphism with inflammatory bowel disease. Clin Gastroenterol Hepatol 5:977–981. doi:10.1016/j.cgh.2007.05.002 PubMedCrossRef

10.

Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 14:143–149PubMed

11.

Bignon JD, Fernandez-Vina MA (1997) Protocols of the 12th International Histocompatibility Workshop for typing of HLA class II alleles by DNA amplification by the polymerase chain reaction (PCR) and hybridization with sequence specific oligonucleotide probes (SSOP). In: Charron D (ed) Genetic diversity of HLA: functional and medical implications. EDK, Paris, pp 584–595

12.

Kotsch K, Wehling J, Blasczyk R (1999) Sequencing of HLA class II genes based on the conserved diversity of the non-coding regions: sequencing based typing of HLA-DRB genes. Tissue Antigens 53:486–497. doi:10.1034/j.1399-0039.1999.530505.x PubMedCrossRef

13.

Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30:1205–1213. doi:10.1002/art.1780301102 PubMedCrossRef

14.

Hedrick PW (1987) Gametic disequilibrium measures: proceed with caution. Genetics 117:331–341PubMed

15.

Hedrick P, Kumar S (2001) Mutation and linkage disequilibrium in human mtDNA. Eur J Hum Genet 9:969–972. doi:10.1038/sj.ejhg.5200735 PubMedCrossRef

16.

Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989. doi:10.1086/319501 PubMedCrossRef

17.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, Nimmo ER, Drummond H, Onnie CM, Prescott NJ, Sanderson J, Bredin F, Berzuini C, Forbes A, Lewis CM, Cardon L, Deloukas P, Jewell D, Mathew CG, Parkes M, Satsangi J (2007) IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology 132:1657–1664. doi:10.1053/j.gastro.2007.02.051 PubMedCrossRef

18.

Sanchez E, Rueda B, Callejas JL, Sabio JM, Ortego-Centeno N, Jimenez-Alonso J, Lopez-Nevot MA, Martin J (2007) Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus. Tissue Antigens 70:233–237. doi:10.1111/j.1399-0039.2007.00881.x PubMedCrossRef

19.

Buning C, Schmidt HH, Molnar T, De Jong DJ, Fiedler T, Buhner S, Sturm A, Baumgart DC, Nagy F, Lonovics J, Drenth JP, Landt O, Nickel R, Buttner J, Lochs H, Witt H (2007) Heterozygosity for IL23R p.Arg381Gln confers a protective effect not only against Crohn’s disease but also ulcerative colitis. Aliment Pharmacol Ther 26:1025–1033PubMedCrossRef

20.

Kastelein RA, Hunter CA, Cua DJ (2007) Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol 25:221–242. doi:10.1146/annurev.immunol.22.012703.104758 PubMedCrossRef

21.

Iwakura Y, Ishigame H (2006) The IL-23/IL-17 axis in inflammation. J Clin Invest 116:1218–1222. doi:10.1172/JCI28508 PubMedCrossRef

22.

Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725. doi:10.1016/S1074-7613(00)00070-4 PubMedCrossRef

23.

Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B, Stepankova R, Robinson N, Buonocore S, Tlaskalova-Hogenova H, Cua DJ, Powrie F (2006) Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25:309–318. doi:10.1016/j.immuni.2006.05.017 PubMedCrossRef

24.

McKenzie BS, Kastelein RA, Cua DJ (2006) Understanding the IL-23-IL-17 immune pathway. Trends Immunol 27:17–23. doi:10.1016/j.it.2005.10.003 PubMedCrossRef

25.

Capon F, Di Meglio P, Szaub J, Prescott NJ, Dunster C, Baumber L, Timms K, Gutin A, Abkevic V, Burden AD, Lanchbury J, Barker JN, Trembath RC, Nestle FO (2007) Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum Genet 122:201–206. doi:10.1007/s00439-007-0397-0 PubMedCrossRef

26.

Orozco G, Rueda B, Robledo G, Garcia A, Martin J (2007) Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort. Hum Immunol 68:681–684. doi:10.1016/j.humimm.2007.05.008 PubMedCrossRef

Title: Lack of association between interleukin 23 receptor gene polymorphisms and rheumatoid arthritis susceptibility
Authors: Jeong Ha Park
Yun Jung Kim
Byung Lae Park
Joon Seol Bae
Hyoung Doo Shin
Sang-Cheol Bae
Publication date: 01-05-2009
Publisher: Springer-Verlag
Published in: Rheumatology International / Issue 7/2009
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-008-0770-x

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