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Meta-analysis of the family-based association between the PTPN22 C1858T polymorphism and Type 1 diabetes

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Abstract

The aim of this study was to determine whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) confers susceptibility to type 1 diabetes (T1D). We conducted a meta-analysis of the transmission disequilibrium test (TDT) examining preferential transmission of the T allele of the PTPN22 C1858T polymorphism to children with T1D. A total of 11 studies were included in this meta-analysis, which contained 3,946 families and 2,024 transmissions of the PTPN22 T allele in 11 European populations. The frequencies of the transmitted and non-transmitted T allele were 1,250 (61.8 %) and 774 (38.2 %), respectively. The T allele was transmitted to T1D offspring more often than expected. Meta-analysis showed a significant association between the PTPN22 T allele and T1D (OR 1.611, 95 % CI 1.421, 1.827, p < 1 × 10−8) without between-study heterogeneity (I2 = 32.5, p = 0.138). Publication bias was observed in this meta-analysis (Egger’s regression test, p-values = 0.061), but the adjusted OR calculated using the trim and fill technique remained significant (OR 1.577, 95 % CI 1.392, 1.785). This meta-analysis of TDT confirms that the PTPN22 C1858T polymorphism is associated with T1D susceptibility in Europeans.

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References

  1. Noble JA, Erlich HA (2012) Genetics of type 1 diabetes. Cold Spring Harb Perspect Med 2(1):a007732

  2. Cohen S, Dadi H, Shaoul E, Sharfe N, Roifman CM (1999) Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Blood 93:2013–2024

    PubMed  CAS  Google Scholar 

  3. Cloutier JF, Veillette A (1999) Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. J Exp Med 189:111–121

    Article  PubMed  CAS  Google Scholar 

  4. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 36:337–338

    Article  PubMed  CAS  Google Scholar 

  5. Peng H, Zhou M, Xu WD, Xu K, Zhai Y, Li R, Wang W, Zhang YJ, Liu SS, Pan HF, Ye DQ (2012) Association of PTPN22 C1858T polymorphism and type 1 diabetes: a meta-analysis. Immunol Invest 41:484–496

    Google Scholar 

  6. Spielman RS, McGinnis RE, Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 52:506–516

    PubMed  CAS  Google Scholar 

  7. Lavrikova E, Nikitin AG, Seregin Iu A, Zil’berman LI, Tsitlidze NM, Kuraeva TL, Peterkova VA, Dedov II, Nosikov VV (2009) Association of the C1858T polymorphism of the PTPN22 gene with type 1 diabetes. Mol Biol (Mosk) 43:1040–1043

    Article  Google Scholar 

  8. Zoledziewska M, Perra C, Orru V, Moi L, Frongia P, Congia M, Bottini N, Cucca F (2008) Further evidence of a primary, causal association of the PTPN22 620W variant with type 1 diabetes. Diabetes 57:229–234

    Article  PubMed  CAS  Google Scholar 

  9. Chelala C, Duchatelet S, Joffret ML, Bergholdt R, Dubois-Laforgue D, Ghandil P, Pociot F, Caillat-Zucman S, Timsit J, Julier C (2007) PTPN22 R620W functional variant in type 1 diabetes and autoimmunity related traits. Diabetes 56:522–526

    Article  PubMed  CAS  Google Scholar 

  10. 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 Immunity 6:459–461

    Article  PubMed  CAS  Google Scholar 

  11. Ladner MB, Bottini N, Valdes AM, Noble JA (2005) Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with type 1 diabetes. Hum Immunol 66:60–64

    Article  PubMed  CAS  Google Scholar 

  12. Smyth D, Cooper JD, Collins JE, Heward JM, Franklyn JA, Howson JM, Vella A, Nutland S, Rance HE, Maier L, Barratt BJ, Guja C, Ionescu-Tirgoviste C, Savage DA, Dunger DB, Widmer B, Strachan DP, Ring SM, Walker N, Clayton DG, Twells RC, Gough SC, Todd JA (2004) Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes 53:3020–3023

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2006) Association of TNF-alpha −308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int 27:157–161

    Article  PubMed  CAS  Google Scholar 

  15. Lee YH, Harley JB, Nath SK (2006) Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet 14:364–371

    Article  PubMed  CAS  Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  17. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56:455–463

    Article  PubMed  CAS  Google Scholar 

  18. Davey Smith G, Egger M (1997) Meta-analyses of randomised controlled trials. Lancet 350:1182

    Article  PubMed  CAS  Google Scholar 

  19. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315:1533–1537

    Article  PubMed  CAS  Google Scholar 

  20. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  21. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  22. Onengut-Gumuscu S, Buckner JH, Concannon P (2006) A haplotype-based analysis of the PTPN22 locus in type 1 diabetes. Diabetes 55:2883–2889

    Article  PubMed  CAS  Google Scholar 

  23. Gregersen PK, Lee HS, Batliwalla F, Begovich AB (2006) PTPN22: setting thresholds for autoimmunity. Semin Immunol 18:214–223

    Article  PubMed  CAS  Google Scholar 

  24. Lee HS, Korman BD, Le JM, Kastner DL, Remmers EF, Gregersen PK, Bae SC (2009) Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations. Arthritis Rheum 60:364–371

    Article  PubMed  CAS  Google Scholar 

  25. Ban Y, Tozaki T, Taniyama M, Tomita M (2005) The codon 620 single nucleotide polymorphism of the protein tyrosine phosphatase-22 gene does not contribute to autoimmune thyroid disease susceptibility in the Japanese. Thyroid 15:1115–1118

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by a grant from the Korea University Medical Center.

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The authors have no financial or non-financial conflicts of interest to declare.

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  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, Korea

    Young Ho Lee & Gwan Gyu Song

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  1. Young Ho Lee
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  2. Gwan Gyu Song
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Correspondence to Young Ho Lee.

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Lee, Y.H., Song, G.G. Meta-analysis of the family-based association between the PTPN22 C1858T polymorphism and Type 1 diabetes. Mol Biol Rep 40, 211–215 (2013). https://doi.org/10.1007/s11033-012-2051-8

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  • DOI: https://doi.org/10.1007/s11033-012-2051-8

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