20.    Severe alopecia areata is associated with a functional polymorphism in the PTPN22 gene.
Helen Kemp(1), Andrew McDonagh(2), David Wengraf(3), Andrew Messenger(2), David Gawkrodger(2), Michael Cork(3), Rachid Tazi-Ahnini(3),  1.Division of Clinical Sciences, University of Sheffield, 2. Dept of Dermatology, Royal Hallamshire Hospital, Sheffield, 3. Division of Molecular & Genetic Medicine, University of Sheffield, Sheffield, UK.

Recently, the non-synonymous C1858T substitution in the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (LYP), has been shown to be associated with susceptibility to a range of autoimmune disorders including vitiligo, type I diabetes mellitus and rheumatoid arthritis. LYP has an important role in negative control of T-cell activation and in T-cell development and is therefore a plausible candidate for involvement in the pathogenesis of AA. The C1858T substitution gives rise to an amino acid change from Arg to Trp at position 620. The objective of this study was to determine whether the disease-associated PTPN22 1858T (W620) allele was also associated with AA. The allelic distribution of the PTPN22 C1858T alleles was determined in 196 English patients with alopecia areata and 507 ethnically matched control subjects. The frequency of the 1858T allele did not differ significantly between the AA patients and the control group. In the cases, out of a total of 392 alleles, 41 (10.5%) encoded the W620 variant compared to 86 of 1014 (8.5%) in the control group. However, in patients with severe disease, 25/168 (14.9%) alleles were 1858T and this frequency differed from that in the control group (P=0.0127). These results suggest that the LYP non-synonymous R620W substitution may have an influence on the severity of alopecia areata and provide further evidence for autoimmunity as an aetiological factor in this condition.