title: The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease.
abstract: The lymphoid tyrosine phosphatase (LYP), encoded by the protein tyrosine phosphatase-22 (PTPN22) gene, is a powerful inhibitor of T cell activation. Recently, a single nucleotide polymorphism (SNP), encoding a functional arginine to tryptophan residue change at LYP codon 620 has been shown to be associated with type 1 diabetes and other autoimmune disorders. We have used a PCR-restriction fragment (XcmI) assay to examine genotypes at the codon 620 polymorphism in 549 unrelated probands with Graves' disease, 104 unrelated subjects with autoimmune Addison's disease and 429 controls. The T nucleotide at the SNP, encoding the tryptophan 620 residue, was present in 151 of 1098 (13.8%) Graves' disease alleles compared to 67 of 858 (7.8%) control alleles (chi(2) = 17.2, p = 3.4 x 10(-5)' odds ratio = 1.88, 5-95% confidence intervals [CI] 1.39 to 2.55). Similarly, the T nucleotide at the codon 620 SNP was present in 26 of 208 (12.5%) Addison's disease alleles vs 7.8% of controls (chi(2) = 4.63, p = 0.031; odds ratio = 1.69, 5-95% CI 1.04 to 2.73). These data suggest that this LYP polymorphism is a susceptibility allele for Graves' disease with a major effect, and which is likely to have a role in many other autoimmune conditions.
authors.affiliation: Institute of Human Genetics, University of Newcastle upon Tyne NE1 3BZ, United Kingdom.
authors.forename: M R
authors.initials: MR
authors.lastname: Velaga
authors.forename: V
authors.initials: V
authors.lastname: Wilson
authors.forename: C E
authors.initials: CE
authors.lastname: Jennings
authors.forename: C J
authors.initials: CJ
authors.lastname: Owen
authors.forename: S
authors.initials: S
authors.lastname: Herington
authors.forename: P T
authors.initials: PT
authors.lastname: Donaldson
authors.forename: S G
authors.initials: SG
authors.lastname: Ball
authors.forename: R A
authors.initials: RA
authors.lastname: James
authors.forename: R
authors.initials: R
authors.lastname: Quinton
authors.forename: P
authors.initials: P
authors.lastname: Perros
authors.forename: S H S
authors.initials: SH
authors.lastname: Pearce
mesh_terms: D000224:Addison Disease / Q000235:genetics; D000483:Alleles; D003062:Codon; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology*; D020641:Polymorphism, Single Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D014364:Tryptophan / Q000235:genetics
chemical_list: D003062:Codon; D014364:Tryptophan; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases