1. ¹Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
2. ²Population Pharmacogenetics Group, Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
3. ³King's College London, St John's Institute of Dermatology, St Thomas's Hospital, London, UK
4. ⁴King's College, Department of Medical and Molecular Genetics, London, UK
5. ⁵Dermatopharmacology Unit, The Dermatology Center, University of Manchester, Hope Hospital, Manchester, UK
6. ⁶Department of Dermatology, Western Infirmary, Glasgow, UK
7. ⁷Department of Clinical Medicine, Institute of Molecular Medicine Trinity College Dublin, Dublin, Ireland
8. ⁸Genetic Repository in Ireland for Psoriasis and Psoriatic Arthritis (GRIPsA), St Vincent's University Hospital, Elm Park, Dublin, Ireland
9. ⁹Department of Dermatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland
10. ¹⁰Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland
11. ¹¹Department of Rheumatology, Adelaide and Meath Hospital incorporating the National Children's Hospital, Tallaght, Dublin, Ireland
12. ¹²Department of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland

Correspondence: Dr Irwin McLean, Human Genetics Unit, University of Dundee, Dundee DD1 9SY, UK. E-mail: w.h.i.mclean@dundee.ac.uk

Received 2 November 2006; Revised 12 December 2006; Accepted 14 January 2007; Published online 5 April 2007.

Abstract

Psoriasis is a common skin disease with an etiology consistent with a multifactorial trait. Several psoriasis susceptibility loci are known, a number of which are also implicated in a predisposition to atopic dermatitis (AD), including the epidermal differentiation complex on chromosome 1q21. It has recently been shown in several replicate studies that prevalent null alleles for the filaggrin gene (FLG) on 1q21 are an important genetic factor in AD. Here, we examined the role of these FLG variants in psoriasis using case:control association studies comparing Irish and UK psoriasis cohorts (combined n=691) to ethnically matched populations (combined n=2117). No association was present for the two common European FLG mutations R501X and 2282del4 (combined ² P=0.989). In addition, the 3' end of the FLG open-reading frame was sequenced in a number of patients with differing types of psoriasis (plaque, guttate, palmoplantar, and late-onset), which excluded the possibility of a gain-of-function frameshift mutation such as those found in loricrin or certain keratin genes. These data suggest that FLG mutations are unlikely to be involved in genetic susceptibility to psoriasis and implies that there may be within-locus heterogeneity in chromosomal regions involved in both AD and psoriasis.