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OBJECTIVE: Protein tyrosine phosphatases (PTPs), such as PTPN22, are important regulators of signal transduction from the T cell receptor and have been associated with autoimmunity. PTPN12 interacts with the same T cell activation accessory molecules, Grb2 and Csk kinase, as the Graves' disease (GD) associated PTPN22 encoded lymphoid tyrosine phosphatase (LYP) molecule and also plays a key role in T cell receptor signalling, leading to the hypothesis that it too may be involved in GD susceptibility. DESIGN: PTPN12 was tested for association in a large well-characterized UK Caucasian case control cohort using seven tagging single nucleotide polymorphisms (SNPs). Patients A total of 1058 GD patients and 864 controls. Measurements Tests for association with the disease. RESULTS: Despite adequate statistical power to detect an effect if present, none of the seven tag SNPs were associated with GD (P = 0.925-0.089). Three SNPs (rs1468682, rs4729535 and rs17467232), however, demonstrated association with the presence of ophthalmopathy NOSPECS classes 2-4 (P = 0.039-0.004). Four SNPs (rs1468682, rs4729535, rs17155601 and rs17467232) revealed evidence of interaction with the previously associated thyrotropin hormone receptor (TSHR) rs2268458 SNP (P = 0.035-0.002). CONCLUSIONS: No association was detected between individual PTPN12 tag SNPs and GD but preliminary evidence suggests PTPN12 confers an increased risk of mild/moderate ophthalmopathy (NOSPECS classes 2-4) and that PTPN12 interacts with the TSHR. Replication of these preliminary results is now required in larger independent datasets to validate these findings.

Original publication

DOI

10.1111/j.1365-2265.2007.02942.x

Type

Journal article

Journal

Clin Endocrinol (Oxf)

Publication Date

11/2007

Volume

67

Pages

663 - 667

Keywords

Case-Control Studies, Chi-Square Distribution, European Continental Ancestry Group, Gene Frequency, Genetic Markers, Genetic Predisposition to Disease, Genotype, Graves Ophthalmopathy, Humans, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatase, Non-Receptor Type 12, Receptors, Thyrotropin