The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease.
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.
Velaga
M R
MR
Institute of Human Genetics, University of Newcastle upon Tyne NE1 3BZ, United Kingdom.
Wilson
V
V
Jennings
C E
CE
Owen
C J
CJ
Herington
S
S
Donaldson
P T
PT
Ball
S G
SG
James
R A
RA
Quinton
R
R
Perros
P
P
Pearce
S H S
SH
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
D003062:Codon; D014364:Tryptophan; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases