Endocrine Abstracts (2006) 11 P880

Do SNPs within the PTPN22 gene contribute to autoimmune disease via different mechanisms?

J Heward, M Simmonds, JA Franklyn & SC Gough

University of Birmingham, Birmingham, West Midlands, United Kingdom.

Graves’ disease (GD) is an autoimmune disorder of the thyroid gland. Autoimmune diseases cluster within families and individuals, leading to the hypothesis of common autoimmunity genes being shared between diseases. This has been confirmed through studies demonstrating association of the HLA region, the CTLA-4 gene and the PTPN22 gene with many disorders including GD and rheumatoid arthritis (RA). We and others have confirmed highly significant association of the R620W SNP of the PTPN22 gene with GD. Recent analysis of 37 SNPs in or near the PTPN22 gene in a cohort of patients with RA, revealed strong associations of further SNPs, some of which seem to be independent of the association seen with the R620W SNP. The aim of this study was to assess these novel RA-associated SNPs with GD in a case control cohort consisting of 768 GD patients and 768 controls. All subjects were UK white Caucasians and all gave informed written consent. The study was approved by the local ethics committee. Five haplotype tagged SNPs were selected for this study and were genotyped using Taqman® technology on an ABI 7900HT. No association of any of these SNPs was seen with GD at either the allelic (P=0.292–0.815) or genotypic (P=0.458–0.7) levels despite having greater than 99% power to detect an effect if present. Lack of replication may be attributed to the different geographical origins of the datasets used. Whilst both were white Caucasian, those in the RA study were from North America, whereas our dataset consisted of patients from the UK. However, it seems more likely that, although the PTPN22 gene appears to be acting as a general autoimmunity locus, the association of different SNPs with RA and GD suggests the mechanisms by which PTPN22 confers susceptibility may in part be disease specific.

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