Genetic susceptibility to psoriasis in Sweden

Abstract

A common skin disease affecting about 2-3% of the population, psoriasis has an inheritance pattern that is unclear, but most probably many genes are involved in its pathogenesis. Other studies have suggested many susceptibility regions in the genome, but as yet independent studies have replicated only some of these regions located on chromosome 1q, 6p and 17q.In searching for psoriasis candidate regions, we analysed a large Swedish psoriasis material that comprised 104 families; in each of which both parents were healthy but two or more siblings were affected with psoriasis. We amplified polymorphic microsatellite markers with PCR technology; the fragments were separated on an ABI 377 sequencer. Having made a statistical linkage analysis that defined regions of interest for further investigation, we could show strong evidence that there is a psoriasis susceptibility region at chromosome 6p (HLA region) and also narrow the region by showing evidence for allelic association to one of the markers (TNFb). We made a stratified genome scan of families in which both psoriasis and joint complaints occurred. The HLA region on chromosome 6p showed stronger linkage in the group without joint complaints. The region on chromosome 17q noted above showed strong linkage in the joint-complaint cohort. Other suggested susceptibility regions on chromosome 1q and 4q showed no linkage in our material. On chromosome 3q21, we also identified a novel region that was linked to joint-complaint families. This chromosomal region was confirmed through stratification of families from south-western Sweden. An independent material (148 families) also confirmed the finding. In an allelic association test, we obtained a significant deviation at markers D3S1269 and D3S1551 that suggests a geographically isolated mutation is present among individuals having joint complaints. This psoriasis susceptibility locus on chromosome 3q21 has been denoted PSORS5. We investigated two candidate genes involved in the proliferation of T-cells, CD80 and CD86, that are located in the chromosome 3q21 region. In the coding or promotor sequence, we found no evidence for mutation in either gene, which suggests neither is responsible for any occurrence of psoriasis.