116 Interleukin-1 Variants in Alopecia Areata: Association Analysis of Disease Severity and Therapeutic Response to Diphenylcyclopropenone.

12R Tazi-Ahnini, 2AJG McDonagh, 1A Cox, 2AG Messenger, 1GW Duff, 12MJ Cork. 1Division of Genomic Medicine, 2Department of Dermatology, Royal Hallamshire Hospital, University of Sheffield, UK

Alopecia areata (AA) is a reversible hair loss disorder with a major genetic component. It is characterised by focal inflammatory lesions with perifollicular T-cell infiltrates, reflecting the role of local cytokine production in the pathogenesis. IL-1alpha and IL-1beta are important inhibitors of hair growth in vitro and their effect is opposed by the interleukin-1 receptor antagonist. IL-1 cluster genes are therefore candidate genes in AA. To investigate the role of the IL-1 system in AA, we examined three biallelic polymorphisms (IL1A+4845, IL1B+3954 & IL1B-511) in 165 patients and 1145 matched controls. In contrast with a previous report (1), we found no significant association of IL1B-511 or IL1B+3954 genotypes with disease in the overall dataset, or on stratification by disease severity or age at onset. Moreover, the power of the earlier study was low, around 41%, while our study has approximately 90% power to detect such an effect. However, there was an association of marginal significance with IL1A+4845 and AA in the overall dataset [odds ratio 1.39, (95% CI 1.00, 1.93)]. This was due mainly to the contribution from mild cases of AA (patchy disease), suggesting that IL-1alpha may have a particular role in the pathogenesis of this subgroup. Diphenylcyclopropenone (DPCP) is used for topical immunotherapy in AA but it is an inconvenient treatment with a low success rate. A test with predictive value for efficacy would be valuable when considering DPCP therapy. The IL1A+4845, IL1B-511 & IL1B+3954 genotypes were analysed in relation to therapeutic response in a subgroup of 60 patients treated with DPCP for at least 6 months. None of the IL1A or IL1B genotypes had predictive value for DPCP response. However, the possibility of an association of IL1A or IL1B genotypes with DPCP response can only be confidently excluded by studying a larger series of patients receiving this treatment. 1. Galbraith GM, et al. 1999. Hum Hered 1999;49:85-9.