PERB11 (MIC): a polymorphic MHC gene is expressed in skin and single nucleotide polymorphisms are associated with psoriasis

The susceptibility genes for psoriasis remain to be identified. At least on e of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ance stral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene (s) could be within a region of at least 4 Mb, most studies have favoured t he area near HLA-B and -C. This region contains a large number of non-HLA g enes, many of which are duplicated and polymorphic. Members of one such gen e family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was pe rformed on 97 patients classified according to age of onset and family hist ory. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (P-c = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism ( SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. P ERB11 is also present in the upper keratin layers but there is relative def iciency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis.