Endocrine Abstracts

Recent genome wide screens performed by the Wellcome Trust Case Control Consortium using 500k single nucleotide polymorphisms (SNP) genotyping arrays have detected several novel susceptibility loci for the common autoimmune diseases (AIDs): Crohn’s disease (CD), type 1 diabetes (T1D) and rheumatoid arthritis (RA). PTPN2, which encodes TCPTP an important negative regulator of inflammation, is one such locus. The rs2542151 SNP in PTPN2 was shown to be highly associated with CD (P=4.6×10⁻⁸), T1D (P=1.9×10⁻⁶) and to a lesser extent RA (P=1.9×10⁻²). When additional screening of this region was performed in T1D, the rs478582 and rs1893217 SNPs were found to have a stronger, independent association with T1D than the rs2542151 SNP (P=9.15×10⁻¹¹ and P=1.16×10⁻¹¹, respectively). These two SNPs were also screened in a large UK Caucasian Graves’ disease (GD) dataset, producing smaller associations (P=2.4×10⁻² and P=2.5×10⁻²). Interestingly, PTPN22, another member of the PTPN family, is also a susceptibility locus for several AIDs. Although association of the R620W SNP within PTPN22 is seen in several AIDs, other disease specific SNP associations unique to GD have been detected. To determine if PTPN2 also contains GD specific associations, screening of the remainder of the PTPN2 region was performed in the aforementioned large UK Caucasian dataset of 2280 GD patients and 2595 matched controls from the 1958 birth cohort using 9 Tag SNPs. All subjects gave informed written consent, and the project was approved by the local ethics committee. Several Tag SNPs were associated with GD (P=2.9×10⁻²–1.46×10⁻³), with some producing larger associations than those previously detected for rs478582 and rs1893217. These data suggest that the largest associations detected in PTPN2 for T1D may in GD be overshadowed by larger disease specific effects. Replication of these results in independent GD and other AID cohorts is required to confirm the GD specific nature of these PTPN2 associated variants.