title: Genetic association between a lymphoid tyrosine phosphatase (PTPN22) and type 1 diabetes.
abstract: The lymphoid-specific phosphatase (LYP) encoded by PTPN22 is involved in preventing spontaneous T-cell activation by dephosphorylating and inactivating T-cell receptor-associated Csk kinase. We have genotyped 396 type 1 diabetic patients and 1,178 control subjects of Caucasian descent from north central Florida and report a strong association between type 1 diabetes and a polymorphism (R620W) in the PTPN22 gene. The homozygous genotype for the T allele encoding the 620W residue is associated with an increased risk for developing type 1 diabetes (odds ratio [OR] = 3.4, P < 0.008), and the heterozygous genotype C/T had an OR of 1.7 (P = 6 x 10(-6)). The C/C homozygous genotype is protective against type 1 diabetes (OR = 0.5, P = 6 x 10(-6)). Furthermore, transmission disequilibrium analysis of 410 affected sibpair and simplex families of Caucasian descent indicated that the type 1 diabetes-associated T allele is transmitted more often (57.2%) than randomly expected (P < 0.003). Together with previous reports of the association between PTPN22 and type 1 diabetes, as well as rheumatoid arthritis and systemic lupus erythematosus, these results provide compelling evidence that LYP is a critical player in multiple autoimmune disorders.
authors.affiliation: Medical College of Georgia, Center for Biotechnology and Genomic Medicine, 1120 15th St., PV6B108, Augusta, GA 30912, USA.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Zheng
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012306:Risk; D044465:White People / Q000235:genetics
chemical_list: C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases