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Preliminary evidence for interaction of PTPN12 polymorphism with TSHR genotype and association with Graves' ophthalmopathy.

Authors: Syed, AA  Simmonds, MJ  Brand, OJ  Franklyn, JA  Gough, SC  Heward, JM 
Citation: Syed AA, etal., Clin Endocrinol (Oxf). 2007 Nov;67(5):663-7. Epub 2007 Jul 3.
Pubmed: (View Article at PubMed) PMID:17608818
DOI: Full-text: DOI:10.1111/j.1365-2265.2007.02942.x

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.


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RGD Object Information
RGD ID: 7829763
Created: 2014-01-23
Species: All species
Last Modified: 2014-01-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.