THE GENETICS OF PSORIASIS - A COMPLEX DISORDER OF THE SKIN AND IMMUNE-SYSTEM

In the last few years, molecular genetics analyses have permitted nove l insights into psoriasis, a disease characterized by uncontrolled pro liferation of keratinocytes and recruitment of T cells into the skin, The disease affects similar to 1-2% of the Caucasian population and ca n occur in association with other inflammatory diseases such as Crohn' s disease and in association with human immunodeficiency virus (HIV) i nfection. Given that psoriasis has characteristics of an autoimmune di sease, it is not surprising that HLA studies revealed an association w ith certain alleles, notably HLA-Cw6, Despite this HLA component, psor iasis in some families is inherited as an autosomal dominant trait wit h high penetrance. Loci at chromosome 17q25 and 4q have been identifie d following genome-wide linkage scans of large, multiply affected fami lies, In the case of at least the susceptibility locus at 17q25, the d evelopment of psoriasis does not require the presence of HLA-Cw6, Sib- pair analyses have confirmed the association with HLA-Cw6, confirmed t he existence of a locus at 17q25 and identified other possible suscept ibility loci. Two independent groups have reported a third region on c hromosome 20p, Despite these findings, the extent of genetic heterogen eity and the role of environmental triggers and modifier genes is stil l not clear. The precise role of HLA also still needs to be defined. T he isolation of novel susceptibility genes will provide insights into the precise biochemical pathways that control this disease. Such pathw ays will also reveal additional candidate genes that can be tested for molecular alterations resulting in disease susceptibility.