A susceptibility gene for psoriatic arthritis maps to chromosome 16q: evidence for imprinting

Abstract

Several genetic loci have been reported for psoriasis, but none has been specifically linked to psoriatic arthritis (PsA), a condition that affects >10% of patients with psoriasis. A genetic component for PsA is suggested by segregation within families and high concordance among identical twins. We performed a linkage scan to map genes contributing to PsA. We identified 178 patients with PsA out of 906 patients who were included in our genetic study of psoriasis. Using a comprehensive genealogy database, we were able to connect 100 of these into 39 families. We genotyped the patients using a framework marker set of 1,000 microsatellite markers, with an average density of 3 cM, and performed multipoint, affected-only, allele-sharing linkage analysis using the Allegro program. On the basis of the initial results, we genotyped more markers for the most prominent loci. A linkage with a LOD score of 2.17 was observed on chromosome 16q. The linkage analysis, conditioned on paternal transmission to affected individuals, gave a LOD score of 4.19, whereas a LOD score of only 1.03 was observed when conditioned for maternal transmission. A suggestive locus on chromosome 16q has previously been implicated in psoriasis. Our data indicate that a gene at this locus may be involved in paternal transmission of PsA.

Figure 1

Genome scan of 39 families with PsA with 1,000-microsatellite framework marker set, in addition to the fine mapping markers in all locations of interest. The multipoint LOD score is shown on the vertical axis; the distance from the p-terminal end of the chromosome (in cM) is shown on the horizontal axis.

Figure 2

Linkage result of 39 families on chromosome 16 with additional markers and considering paternal transmissions only (black line) and maternal transmissions only (red line). The multipoint LOD score is shown on the vertical axis; the distance from the p-terminal end of the chromosome (in cM) is shown on the horizontal axis.