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

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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 21df  = 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.

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Fig. 1

Abbreviations

WTCCC:

Wellcome Trust Case Control Consortium

SNP:

Single nucleotide polymorphism

T1D:

Type 1 diabetes

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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.

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Authors and Affiliations

  1. Immunology Department, Hospital Clínico San Carlos, Martín Lagos s/n, 28040, Madrid, Spain

    Laura Espino-Paisan, Miguel Fernández-Arquero, Maria Ángeles Figueredo, Emilio G. de la Concha, Elena Urcelay & Jose Luis Santiago

  2. Endocrinology Department, Hospital Ramón y Cajal, Carretera Colmenar Viejo KM 9,100, 28049, Madrid, Spain

    Hermenegildo de la Calle

Authors
  1. Laura Espino-Paisan
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  2. Hermenegildo de la Calle
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  3. Miguel Fernández-Arquero
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  4. Maria Ángeles Figueredo
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  5. Emilio G. de la Concha
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  6. Elena Urcelay
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  7. Jose Luis Santiago
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Corresponding author

Correspondence to Laura Espino-Paisan.

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Espino-Paisan, L., de la Calle, H., Fernández-Arquero, M. et al. A polymorphism in PTPN2 gene is associated with an earlier onset of type 1 diabetes. Immunogenetics 63, 255–258 (2011). https://doi.org/10.1007/s00251-010-0500-x

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  • DOI: https://doi.org/10.1007/s00251-010-0500-x

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