Genetics of psoriasis and psoriatic arthritis: a report from the GRAPPA 2010 annual meeting.
Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are interrelated disorders, PsA representing a disease within a disease. From an epidemiological perspective, the genetic contributions of PsV and PsA are now well documented. HLA-C is firmly established as a PsV/PsA gene, with HLA-Cw*0602 as a major risk allele. Fine-mapping studies within the MHC region in PsV and PsA have identified novel loci that are independent of the HLA-Cw6 allele. Recent genome-wide association scans have led to a substantial increase in the number of candidate genes reaching genome-wide significance in PsV and PsA cohorts. Most of these genes can be grouped into an integrated pathogenic model of PsV/psoriatic disease comprising distinct signaling networks affecting skin barrier function (LCE3, DEFB4, GJB2), innate immune responses involving nuclear factor-κB and interferon signaling (TNFAIP3, TNIP1, NFKBIA, REL, FBXL19, TYK2, NOS2), and adaptive immune responses involving CD8 T lymphocytes and interleukin 23 (IL-23)/IL-17-mediated lymphocyte signaling (HLA-C, IL12B, IL23R, IL23A, TRAF3IP2, ERAP1). Further development of a global genetic risk score and inclusion of potential gene/gene and gene/environment interactions will likely enhance the predictive value of recently identified genetic variants.
Memorial University, St. John’s, Newfoundland, Canada. prahman@mun.ca
Proton
P
Rahman
James T
JT
Elder
D056704:Adaptive Immunity / Q000235:genetics; D015535:Arthritis, Psoriatic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D000072259:Connexin 26; D017630:Connexins; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D012867:Skin / Q000276:immunology
D017630:Connexins; C000607042:GJB2 protein, human; D015236:HLA-C Antigens; D000072259:Connexin 26