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A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families

Genes & Immunity volume 5, pages 678–680 (2004)Cite this article

Abstract

Type I diabetes (T1D) is a complex disorder, which arises from the autoimmune destruction of the insulin-secreting β cells of the pancreas leading to a life-long dependence on exogenous insulin. A recent study of T1D cases and controls provided evidence for association between an allele of a functional single-nucleotide polymorphism (SNP) in the PTPN22 gene and T1D. In the current study, this SNP was genotyped in a collection of 406 multiplex T1D families. Significant evidence of the combined presence of association and linkage to T1D was obtained (P=2.5 × 10−5). Linkage studies in subsets of families defined by PTPN22 SNP genotypes suggest possible interaction with loci on chromosomes 3 and 21. Previous genome scans in this collection of T1D families, and others, have not yielded significant evidence of linkage in the region of the PTPN22 locus. However, the highly significant evidence of allelic association suggests that variation at, or near, this functional SNP contributes to the risk of T1D.

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Acknowledgements

We thank V Anne Morrison and Lemuel Navarro for assistance with nucleotide sequencing, Wendy Ankener and James Devlin for assistance with genotyping, and Mary West for assistance with manuscript preparation. This work was supported by grants from the NIH (DK46635) and JDRF (1-2001-433) to PC and from the NIH (DK46618 and DK55277) to RSS.

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Authors and Affiliations

  1. Molecular Genetics Program, Benaroya Research Institute, Seattle, WA, USA

    S Onengut-Gumuscu & P Concannon

  2. Department of Immunology, University of Washington School of Medicine, Seattle, WA, USA

    S Onengut-Gumuscu & P Concannon

  3. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    K G Ewens & R S Spielman

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  1. S Onengut-Gumuscu
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  2. K G Ewens
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  3. R S Spielman
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  4. P Concannon
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Correspondence to P Concannon.

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Onengut-Gumuscu, S., Ewens, K., Spielman, R. et al. A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes Immun 5, 678–680 (2004). https://doi.org/10.1038/sj.gene.6364138

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