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Role of the C1858T polymorphism of protein tyrosine phosphatase non-receptor type 22 (PTPN22) in children and adolescents with type 1 diabetes

The Pharmacogenomics Journal volume 17, pages 186–191 (2017)Cite this article

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Abstract

In recent years, increasing interest has been devoted to the susceptibility gene polymorphisms in type 1 diabetes (T1D) as well as in other autoimmune diseases. Among these, a nucleotide polymorphism of the gene encoding for the protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been associated with T1D in several studies. The aim of this study is to define the frequency of the C1858T polymorphism in the PTPN22 gene in a cohort of 113 Caucasian patients (58 males and 55 females) with T1D, and to assess a possible correlation with a group of clinically relevant variables: age at onset, gender, diabetes-related autoantibodies, residual β-cell function and daily insulin requirement (IR) 6 months after diagnosis. Using a PCR-RFLP approach, we evidenced a 17.7% frequency of the PTPN22 C1858T polymorphism in diabetic patients, higher than the frequency showed in the general population. A statistically significant correlation between this polymorphism and higher levels of C-peptide at diagnosis and lower IR at 6 months from diagnosis was observed (P=0.001 and P=0.04). Moreover, 1858T variant carriers were more frequently positive for glutamic acid decarboxylase (GAD) autoantibodies at diagnosis than wild-type subjects (P=0.19). On the other hand, no significant difference regarding age at onset, gender distribution, insulinoma-associated 2 molecule (IA2) and islet cell antibodies (ICA) positivity was found. These findings, if adequately confirmed in the future and extended to larger samples, may characterize a subset of T1D patients with a defined genetic pattern, who may be eligible for trials aimed to preserve residual β-cell function in the coming years.

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Acknowledgements

We express our gratitude to patients and their families for participating in this study. We also thank Kelly Chuang, MHS, Johns Hopkins University for help with language revision.

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Authors and Affiliations

  1. Department of Pediatrics, 'G. d'Annunzio' University, Chieti, Italy

    A Blasetti, C Di Giulio, S Tumini, D Rapino, L Comegna, G Prezioso, R Chiuri, S Franchini & F Chiarelli

  2. DISPUTer (Department of Psychological Sciences, Laboratory of Molecular Genetics, Health and Territory), School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti, Italy

    M Provenzano & L Stuppia

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  1. A Blasetti
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Blasetti, A., Di Giulio, C., Tumini, S. et al. Role of the C1858T polymorphism of protein tyrosine phosphatase non-receptor type 22 (PTPN22) in children and adolescents with type 1 diabetes. Pharmacogenomics J 17, 186–191 (2017). https://doi.org/10.1038/tpj.2016.6

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