Journal
HUMAN IMMUNOLOGY
Volume 66, Issue 1, Pages 60-64Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2004.09.016
Keywords
PTPN22; type 1 diabetes; polymorphism; genetic susceptibility; transmission disequilibrium test
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Funding
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R56DK061722, R01DK061722] Funding Source: NIH RePORTER
- NIDDK NIH HHS [DK61722, R01 DK061722] Funding Source: Medline
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The PTPN22 (protein tyrosine phosphatase N22) gene encodes the protein tyrosine phosphatase Lyp. One function of Lyp is downregulation of T-cell signaling through its interaction with the negative regulatory kinase C-terminal Src tyrosine kinase (Csk). A single nucleotide polymorphism in the PTPN22 gene, C1858T, encodes products with different Csk binding affinities. Disease association of the PTPN22 1858T allele has been reported in case-control studies of three different autoimmune disorders: type 1 diabetes (T1D), rheumatoid arthritis, and systemic lupus erythematosus. In this study, a set of 341 white, multiplex T1D families were genotyped for the C1858T single nucleotide polymorphism of PTPN22, and transmission disequilibrium test analysis revealed significant association (p = 0.005) of the T allele with T1D. No effects of parent of origin, sex of patient, or human leukocyte antigen genotype (high-risk human leukocyte antigen DR3/DR4 vs non-DR3/DR4) were observed. However, transmission of the T allele was significantly increased in the subset of patients who also carried at least one copy of the TCF7 883A allele, another allele that is important in regulating T-cell responses and that is associated with T1D. These results are consistent with the hypothesis that individuals lacking the C allele of PTPN22 may have reduced capacity to downregulate T-cell responses and may therefore be more susceptible to autoimmunity. Human Immunology 66, 60-64 (2005). (C) American Society for Histocompatibility and Immunogenetics, 2005. Published by Elsevier Inc.
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