Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein tyrosine phosphatase PTPN22 is involved in the negative regulation of T-cell responsiveness. Recently, the association of a coding variant of the PTPN22 gene-R620W(1858C>T) with a number of autoimmune diseases has been described. Therefore, we tested the association of PTPN22 1858*T allele in Dutch early onset type 1 diabetes (T1D) and rheumatoid arthritis (RA) patients, as well as celiac disease (CD) patients, for which no previous study of PTPN22 has been reported. The PTPN22 variant was strongly associated with T1D in cases vs controls (P=2 x 10(-7), OR=2.3, 95% CI=1.7-3.1) as well as in a transmission disequilibrium test in nuclear trio's (P=9 x 10(-9), OR=3.3, CI=2.1-5.0), RA (case/control: P=0.003, OR=1.8 CI =1.2-2.6), but not CD, in spite of a trend of increased homozygosity (P=0.05) and early age at onset (P=0.01). PTPN22 is not generally associated with T-cell mediated autoimmune diseases, although it might play a role in the CD patients with early clinical manifestation.
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PMID:Differential association of the PTPN22 coding variant with autoimmune diseases in a Dutch population. 1587 58

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is the third major locus affecting risk of type I diabetes (T1D), after HLA-DR/DQ and INS. The most associated single-nucleotide polymorphism (SNP), rs2476601, has a C->T variant and results in an arginine (R) to tryptophan (W) amino acid change at position 620. To assess whether this, or other specific variants, are responsible for T1D risk, the Type I Diabetes Genetics Consortium analyzed 28 PTPN22 SNPs in 2295 affected sib-pair (ASP) families. Transmission Disequilibrium Test analyses of haplotypes revealed that all three haplotypes with a T allele at rs2476601 were overtransmitted to affected children, and two of these three haplotypes showed statistically significant overtransmission (P=0.003 to P=5.9E-12). Another haplotype had decreased transmission to affected children (P=3.5E-05). All haplotypes containing the rs2476601 T allele were identical for all SNPs across PTPN22 and only varied at centromeric SNPs. When considering rs2476601 'C' founder chromosomes, a second haplotype (AGGGGC) centromeric of PTPN22 in the C1orf178 region was associated with protection from T1D (odds ratio=0.81, P=0.0005). This novel finding requires replication in independent populations. We conclude the major association of PTPN22 with T1D is likely due to the recognized non-synonymous SNP rs2476601 (R620W).
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PMID:rs2476601 T allele (R620W) defines high-risk PTPN22 type I diabetes-associated haplotypes with preliminary evidence for an additional protective haplotype. 1995 96

Protein tyrosine phosphatases (PTPs) play a central role in modulating the transduction of cellular signals, including the cells of the immune system. Several PTPs, PTPN22, PTPN2, and UBASH3A, have been associated with risk of type 1 diabetes (T1D) by genome wide association studies. Based on the current understanding of PTPs, it is clear that these variants impact antigen receptor signaling and cytokine signaling. This impact likely contributes to the development and progression of autoimmunity through multiple mechanisms, including failures of central and peripheral tolerance and the promotion of proinflammatory T cell responses. In this review, we discuss the genetic and functional implications of two of these PTPs, PTPN22 and PTPN2, in the development of T1D. We describe the known roles of these proteins in immune function, and how the expression and function of these proteins is altered by the genetic variants associated with T1D. Yet, there are still controversies in the field that require further study and the development of new approaches to extend our understanding of these PTP variants, with the goal of using the information gained to improve our ability to predict and cure T1D.
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PMID:Protein tyrosine phosphatases and type 1 diabetes: genetic and functional implications of PTPN2 and PTPN22. 2380 60

Type 1 diabetes mellitus (T1DM) is an autoimmune multifactorial disease. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. PTPN22 C1858T polymorphism was associated with T1DM in populations of Caucasian origin. The aim of this study was the investigation for the first time of the association of PTPN22 C1858T polymorphism with T1DM in Greek population. We studied 130 children and adolescents with T1DM and 135 healthy individuals of Greek origin. The polymorphism was genotyped using polymerase chain reaction with restriction fragment length polymorphism. C1858T and T1858T genotypes as well as 1858T allele were found more frequently in patients (10.8% and 5.8%, resp.) than in healthy individuals (5.9% and 3.0%, resp.) but at non statistically significant level. There was no statistically significant association found with gender, age at diagnosis, severity of onset, history of Hashimoto thyroiditis or family history of T1DM. Increased frequency of 1858T allele in patients than in controls, implying a probable association, agrees with results of similar studies on other populations. The inability to find a statistically significant difference is probably due to the decreased frequency of minor allele in Greek population, indicating the need for a larger sample.
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PMID:The role of PTPN22 C1858T gene polymorphism in diabetes mellitus type 1: first evaluation in Greek children and adolescents. 2393 38

Protein tyrosine phosphatases (PTPs) are a large family of enzymes that generally oppose the actions of protein tyrosine kinases (PTKs). Genetic polymorphisms for particular PTPs are associated with altered risk of both type 1 diabetes (T1D) and type 2 diabetes (T2D). Moreover, recent evidence suggests that PTPs play crucial roles in metabolism. They can act as regulators of liver homeostasis, food intake, or immune-mediated pancreatic b cell death. In this review we describe the mechanisms by which different members of the non-receptor PTP (PTPN) family influence metabolic physiology. This 'metabolic job' of PTPs is discussed in depth and the role of these proteins in different cell types compared. Understanding the pathways regulated by PTPs will provide novel therapeutic strategies for the treatment of diabetes.
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PMID:Protein tyrosine phosphatases: molecular switches in metabolism and diabetes. 2543 62