The Genetics of Psoriasis, Psoriatic Arthritis and Atopic Dermatitis

Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin associated with various immunologic abnormalities. Approximately 30% of psoriasis patients also have joint involvement, indicative of psoriatic arthritis. Genes and environment play a key role in the pathogenesis of these diseases. Genome-wide linkage scans have identified multiple loci linked to each disease and revealed overlap with psoriasis and atopic dermatitis susceptibility loci on chromosomes 1q21, 3q21, 17q25 and 20p12. The genes from these loci have not yet all been identified, or systematically tested for a role in psoriasis and atopic dermatitis; however, these locations suggest that some susceptibility factors lie within genes or gene families with common effects upon epithelial immunity. A strong HLA association is described for psoriasis, but not for atopic dermatitis. Knowledge of the genetic factors leading to these diseases will lead to an understanding of their variable age at onset, their waxing and waning and the variability of body surface environment. The effect of environmental triggers may also be understood once the altered pathways are elucidated. Genes implicated so far in atopic dermatitis are SPINK5, FcepsilonRI-beta and PHF11. Genes implicated in psoriasis so far are HLA-C, SLC9A3R1, NAT9, RAPTOR and SLC12A8. Genetic modifiers such as CARD15 may predispose to psoriatic arthritis.