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A PTPN22 promoter polymorphism −1123G>C is associated with RA pathogenesis in Chinese

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Abstract

The minor allele of the non-synonymous single nucleotide polymorphism (SNP) +1858C>T within the PTPN22 gene has now been unequivocally confirmed as conferring susceptibility to RA in population from Europe and America, but not in population from Asia. The aim of this study was to jointly address and integrate these separate findings to further elucidate the association between the PTPN22 gene and RA in Chinese Hans of Guangdong province. Four hundred and ninety-four cases with RA and 496 healthy controls were randomly selected, their SNPs at position −1123G>C (rs2488457), +1858C>T (rs2476601), +788G>A (rs33996649), and rs1310182 were genotyped using PCR–RFLP, followed by agarose gel electrophoresis. +1858C>T (rs2476601) and +788G>A (rs33996649) are not polymorphic in Chinese Hans. Meanwhile, our result reveals that the degree of association between the promoter polymorphism, −1123G>C and RA, was analogous to that observed in Japanese reports (odds ratio [OR] = 1.517, 95% CI = [1.154–1.995], P = 0.003). Expression study also indicated a tendency for association between −1123G>C and PTPN22 gene expression. Our study underpins that the promoter polymorphism, −1123G/C, may be a causal SNP for RA in Asian.

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References

  1. Deighton CM, Walker DJ, Griffiths ID, Roberts DF (1989) The contribution of HLA to rheumatoid arthritis. Clin Genet 36:178–182

    Article  PubMed  CAS  Google Scholar 

  2. Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC et al (2004) A missense single nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75:330–337

    Article  PubMed  CAS  Google Scholar 

  3. Plenge RM, Padyukov L, Remmers EF, Purcell S, Lee AT, Karlson EW et al (2005) Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Am J Hum Genet 77:1044–1060

    Article  PubMed  CAS  Google Scholar 

  4. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK et al (2007) The PTPN22 C1858T functional polymorphism and autoimmune diseases a meta-analysis. Rheumatology (Oxford) 46:49–56

    Article  CAS  Google Scholar 

  5. Mustelin T, Vang T, Bottini N (2005) Protein tyrosine phosphatases and the immune response. Nat Rev Immunol 5:43–57

    Article  PubMed  CAS  Google Scholar 

  6. Matthews RJ, Bowne DB, Flores E, Thomas ML (1992) Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of aphosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol Cell Bio l12:2396–2405

    Google Scholar 

  7. Bottini N, Musumeci L, Alonso A et al (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 36:337–338

    Article  PubMed  CAS  Google Scholar 

  8. Sahin N, Bicakcigil M, Atagunduz P, Direskeneli H (2007) SaruhanDireskeneli G PTPN22 gene polymorphism in Behcet’s disease. Tissue Antigens 70:432–434

    Article  PubMed  CAS  Google Scholar 

  9. Sahin N, Aksu K, Kamali S et al (2008) PTPN22 gene polymorphism in Takayasu’s arteritis. Rheumatology (Oxford) 47:634–635

    Article  CAS  Google Scholar 

  10. Zheng W, She JX (2005) Genetic association between a lymphoid tyrosine phosphatase (PTPN22) and type 1 diabetes. Diabetes 54:906–908

    Article  PubMed  CAS  Google Scholar 

  11. Mori M, Yamada R, Kobayashi K, Kawaida R, Yamamoto K (2005) Ethnic differences in allele frequency of autoimmune-disease-associated SNPs. J Hum Genet

  12. Kawasaki E, Awata T, Ikegami H, Kobayashi T, Maruyama T, Nakanishi K et al (2006) Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): association between a promoter polymorphism and type 1 diabetes in Asian populations. Am J Med Genet A 140:586–593

    PubMed  Google Scholar 

  13. Victoria EHC, Xiaolan H, Anand PC, Steven JS et al (2005) PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. Am J Hum Genet 77:567–581

    Article  Google Scholar 

  14. Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  15. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  PubMed  CAS  Google Scholar 

  16. Kenneth JL, Thomas DS (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  Google Scholar 

  17. Hinks A, Barton A, John S et al (2005) Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis Rheum 52:1694–1699

    Article  PubMed  CAS  Google Scholar 

  18. Seldin MF, Shigeta R, Laiho K et al (2005) Finnish case–control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis. Genes Immun 6:720–722

    PubMed  CAS  Google Scholar 

  19. Pierer M, Kaltenhauser S, Arnold S et al (2006) Association of PTPN22 1858 single nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients. Arthritis Res Ther 8:R75

    Article  PubMed  Google Scholar 

  20. Zhernakova A, Eerligh P, Wijmenga C, Barrera P, Roep BO, Koeleman BP (2005) Differential association of the PTPN22 coding variant with autoimmune diseases in a Dutch population. Genes Immun 6:459–461

    Article  PubMed  CAS  Google Scholar 

  21. Orozco G, Sanchez E, Gonzalez Gay MA et al (2005) Association of a functional single nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Rheum 52:219–224

    Article  PubMed  CAS  Google Scholar 

  22. van Oene M, Wintle RF, Liu X et al (2005) Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn’s disease, in Canadian populations. Arthritis Rheum 52:1993–1998

    Article  PubMed  Google Scholar 

  23. Ikari K, Momohara S, Inoue E et al (2006) Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population. Rheumatology 45:1345–1348

    Article  PubMed  CAS  Google Scholar 

  24. Viken MK, Olsson M, Flåm ST, Førre Ø, Kvien TK, Thorsby E, Lie BA (2007) The PTPN22 promoter polymorphism −1123G>C association cannot be distinguished from the 1858C>T association in a Norwegian rheumatoid arthritis material. Tissue Antigens 70(3):190–197

    Article  PubMed  CAS  Google Scholar 

  25. Comings DE, MacMurray JP, Gonzalez N, Ferry L, Peters WR (1999) Association of the serotonin transporter gene with serum cholesterol levels and heart disease. Mol Genet Metab 67:248–253

    Article  PubMed  CAS  Google Scholar 

  26. Pooley EC, Fairburn CG, Cooper Z, Sodhi MS, Cowen PJ, Harrison PJ (2004) A 5-HT2C receptor promoter polymorphism (HTR2C–759C/T) is associated with obesity in women, and with resistance to weight loss in heterozygotes. Am J Med Genet Part B Neuropsychiatr Genet 126B:124–127

    Article  Google Scholar 

  27. Comings DE, Gonzalez NS, Cheng Li SC, MacMurray J (2003) A “line item’’ approach to the identification of genes involved in polygenic behavioral disorders: the adrenergic a2A(ADRA2A) gene. Am J Med Genet Part B Neuropsychiatr Genet 118B:110–114

    Article  CAS  Google Scholar 

  28. Owen MS, Lisa AM, Ade `le LY et al (2007) Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions. Immunity 27:912–926

    Article  Google Scholar 

  29. Juliger S, Bongartz M, Luty AJ, Kremsner PG, Kun JF (2003) Functional analysis of a promoter variant of the gene encoding the interferon-gamma receptor chain I. Immunogenetics 54:675–680

    PubMed  Google Scholar 

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Acknowledgments

The study is supported by Natural Science Foundation of Guangdong Province (project no: 8151051501000089).

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The authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Laboratory, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China

    Jian-Jun Huang, Yu-Rong Qiu, Hai-Xia Li, De-Hua Sun, Jia Yang & Chun-Li Yang

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  1. Jian-Jun Huang
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  2. Yu-Rong Qiu
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  3. Hai-Xia Li
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  4. De-Hua Sun
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Correspondence to Yu-Rong Qiu.

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Huang, JJ., Qiu, YR., Li, HX. et al. A PTPN22 promoter polymorphism −1123G>C is associated with RA pathogenesis in Chinese. Rheumatol Int 32, 767–771 (2012). https://doi.org/10.1007/s00296-010-1705-x

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  • DOI: https://doi.org/10.1007/s00296-010-1705-x

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