The genetic basis of psoriasis

For a complex genetic disease, psoriasis has a high penetration within families and a concordance rate of up to 70% in identical twins. Despite this and the endeavors of many research groups for more than a decade, no susceptibility allele has so far been unequivocally identified, although about 20 genetic loci associated with psoriasis have been reported from linkage-based studies. Moreover, only 1 of these linkage-based loci, PSORS1, that includes the HLA-C gene on chromosome 6p21, has been universally confirmed. Very recent data strongly indicate that HLA-Cw*0602 is the susceptibility allele in this locus, a finding that is consistent with the notion that the pathogenesis of psoriasis involves autoantigen recognition by epidermal CD8+ T lymphocytes. Several candidate genes in some of the other 7 PSORS designated loci are currently being evaluated. The relative lack of success in elucidating the genetic basis of psoriasis highlights the formidable challenge of dissecting the genetic basis of diseases with a complex mode of inheritance.