F14 INTERLEUKIN-1 GENE CLUSTER POLYMORPHISMS IN ALOPECIA AREATA: STRONG ASSOCIATION OF IL1RN & IL1L1 GENOTYPES WITH SEVERE DISEASE & EARLY AGE AT ONSET.

R Tazi Ahnini, AJG McDonagh, A Cox, FS di Giovine, AG Messenger, P Dimitropoulou, GW Duff & MJ Cork.  University of Sheffield, Sheffield S10 2JF, UK

Alopecia areata is an inflammatory hair loss disease with a major genetic component.  The presence of focal inflammatory lesions with perifollicular T-cell infiltrates reflects the importance of local cytokine production in the pathogenesis.  In addition to its fundamental pro-inflammatory role, the interleukin-1 (IL-1) system has been shown to have major effects on hair growth regulation in vitro, with the inhibitory actions of IL-1a and IL-1b being opposed by the receptor antagonist, IL-1ra.

To test whether the genes encoding these molecules are involved in alopecia areata susceptibility, we examined 5 biallelic polymorphisms within the 430 kbp of the IL-1 gene cluster on chromosome 2q14 (IL1RN+2018, IL1B+3954, IL1B-511, IL1A+4845 & IL1L1+4734) in a case-control association study on 165 patients.  We found no significant association with IL1A+4845, IL1B-511 or IL1B+3954 variants.  However, homozygosity for the rare allele of IL1RN was significantly associated with alopecia areata (OR=1.89, 95% ci (1.09, 3.28); p=0.02) confirming our previous observations of significant association between the IL1RNVNTR and disease.  The results also revealed a novel association with IL1L1+4734.  Genotypes combining 3 copies of the rare alleles at the IL1RN & IL1L1 loci conferred a markedly higher risk of disease (OR=3.37, 95% ci (1.60, 7.06); p=0.001), suggesting a synergetic effect between these genes.  This effect was stronger in patients with severe disease (alopecia totalis/ universalis) (OR 4.62, 95% ci  (1.87, 11.40), p=0.0022).  The highest risk was found in patients with early age at onset (<20 years) (OR=6.38, 95% ci (2.64, 15.42), p=0.0002).

Our results suggest that these polymorphisms within IL1L1 & IL1RN themselves or a gene in linkage disequilibrium with IL1L1 & IL1RN predispose to the severe form of alopecia areata.