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Immunogenetics

, Volume 63, Issue 4, pp 255–258 | Cite as

A polymorphism in PTPN2 gene is associated with an earlier onset of type 1 diabetes

  • Laura Espino-Paisan
  • Hermenegildo de la Calle
  • Miguel Fernández-Arquero
  • Maria Ángeles Figueredo
  • Emilio G. de la Concha
  • Elena Urcelay
  • Jose Luis Santiago
Brief Communication

Abstract

The Wellcome Trust Case Control Consortium (WTCCC) genome-wide study found association of PTPN2 with three autoimmune diseases, among them is type 1 diabetes (T1D). This result was confirmed by a follow-up study that pointed to new independent signals within the region. However, both studies were performed in patients with an early-onset T1D. We aimed at replicating the previous results and studying the influence of these polymorphisms in the age at T1D debut. We genotyped 439 T1D Spanish subjects (age at onset, 1 to 65 years) and 861 controls for two PTPN2 single nucleotide polymorphisms (SNPs), rs2542151 and rs478582, and studied the effect of both polymorphisms in age at onset through stratified and continuous analyses. The frequency of rs2542151*G carriers was significantly higher in the early-onset group compared with late-onset patients (p = 0.023) and with controls (OR = 1.61 [1.14–2.26]; p = 0.005). No significant differences were found between controls and late-onset patients. The log-rank chi-square test for the Kaplan–Meier plots (carriers of susceptibility allele vs non carriers) was statistically significant (χ 1df 2  = 4.485; p = 0.034), yielding an earlier disease debut for G carriers. The analysis of the SNP rs478582 did not reach statistical significance. In summary, we replicate the association detected by the WTCCC and propose that the rs2542151*G allele confers risk to an earlier onset of T1D.

Keywords

Type 1 diabetes Susceptibility PTPN2 Age at onset Polymorphism 

Abbreviations

WTCCC

Wellcome Trust Case Control Consortium

SNP

Single nucleotide polymorphism

T1D

Type 1 diabetes

Notes

Acknowledgments

We thank Carmen Martínez and M Angel García-Martínez for expert technical assistance. Jose Luis Santiago is a recipient of FIS contract (CM08/00079). Elena Urcelay works for the “Fundación para la Investigación Biomédica Hospital Clínico San Carlos”.

Conflict of interests

The authors declare that they have no conflict of interest.

References

  1. Doody KM, Bourdeau A, Tremblay ML (2009) T-cell protein tyrosine phosphatase is a key regulator in immune cell signaling: lessons from the knockout mouse model and implications in human disease. Immunol Rev 228:325–341PubMedCrossRefGoogle Scholar
  2. Klemetti P, Savilahti E, Ilonen J, Akerblom HK, Vaarala O (1998) T-cell reactivity to wheat gluten in patients with insulin-dependent diabetes mellitus. Scand J Immunol 47:48–53PubMedCrossRefGoogle Scholar
  3. Klinker MW, Schiller JJ, Magnuson VL, Wang T, Basken J, Veth K, Pearce KI, Kinnunen L, Harjutsalo V, Wang X, Tuomilehto J, Sarti C, Ghosh S (2010) Single-nucleotide polymorphisms in the IL2RA gene are associated with age at diagnosis in late-onset Finnish type 1 diabetes subjects. Immunogenetics 62:101–107PubMedCrossRefGoogle Scholar
  4. Moore F, Colli ML, Cnop M, Esteve MI, Cardozo AK, Cunha DA, Bugliani M, Marchetti P, Eizirik DL (2009) PTPN2, a candidate gene for type 1 diabetes, modulates interferon-gamma-induced pancreatic beta-cell apoptosis. Diabetes 58:1283–1291PubMedCrossRefGoogle Scholar
  5. Santiago JL, Alizadeh BZ, Martinez A, Espino L, de la Calle H, Fernandez-Arquero M, Figueredo MA, de la Concha EG, Roep BO, Koeleman BP, Urcelay E (2008) Study of the association between the CAPSL-IL7R locus and type 1 diabetes. Diabetologia 51:1653–1658PubMedCrossRefGoogle Scholar
  6. Scharl M, Paul G, Weber A, Jung BC, Docherty MJ, Hausmann M, Rogler G, Barrett KE, McCole DF (2009) Protection of epithelial barrier function by the Crohn’s disease associated gene protein tyrosine phosphatase n2. Gastroenterology 137:2030–2040e5PubMedCrossRefGoogle Scholar
  7. Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, Howson JM, Stevens H, McManus R, Wijmenga C, Heap GA, Dubois PC, Clayton DG, Hunt KA, van Heel DA, Todd JA (2008) Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 359:2767–2777PubMedCrossRefGoogle Scholar
  8. Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, Bailey R, Nejentsev S, Field SF, Payne F, Lowe CE, Szeszko JS, Hafler JP, Zeitels L, Yang JH, Vella A, Nutland S, Stevens HE, Schuilenburg H, Coleman G, Maisuria M, Meadows W, Smink LJ, Healy B, Burren OS, Lam AA, Ovington NR, Allen J, Adlem E, Leung HT, Wallace C, Howson JM, Guja C, Ionescu-Tirgoviste C, Simmonds MJ, Heward JM, Gough SC, Dunger DB, Wicker LS, Clayton DG (2007) Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 39:857–864PubMedCrossRefGoogle Scholar
  9. Vaarala O, Klemetti P, Savilahti E, Reijonen H, Ilonen J, Akerblom HK (1996) Cellular immune response to cow’s milk beta-lactoglobulin in patients with newly diagnosed IDDM. Diabetes 45:178–182PubMedCrossRefGoogle Scholar
  10. The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Laura Espino-Paisan
    • 1
  • Hermenegildo de la Calle
    • 2
  • Miguel Fernández-Arquero
    • 1
  • Maria Ángeles Figueredo
    • 1
  • Emilio G. de la Concha
    • 1
  • Elena Urcelay
    • 1
  • Jose Luis Santiago
    • 1
  1. 1.Immunology DepartmentHospital Clínico San CarlosMadridSpain
  2. 2.Endocrinology DepartmentHospital Ramón y CajalMadridSpain

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