Genetic variations associated with psoriasis and psoriatic arthritis found by genome-wide association.
Psoriasis and psoriatic arthritis are immune disorders with a complex polygenic basis. HLA-Cw6, which lies in the major histocompatibility region on chromosome 6, is considered the major genetic determinant of psoriasis. Recent genome-wide association studies have identified new variants outside of the MHC with relevance to the immunology of psoriasis. Variants in or near genes that encode subunits of cytokines (IL12B, IL23A) or cytokine receptors (IL23R) are interesting given that the gene product of IL12B, p40, is the target of a recently approved monoclonal antibody therapy for psoriasis (ustekinumab). Association with psoriasis and psoriatic arthritis has been found in TNFAIP3 and TNFIP1, ubiquitin ligases in the NF-kappaB pathway, and IL13, a Th2 cytokine. Copy number variation of human beta-defensin and late cornified envelope genes also associate with psoriasis. Many of these genetic variations also associate with immune disorders considered psoriatic co-morbidities, including Crohn's disease and diabetes.
Duffin
Kristina Callis
KC
4A330 School of Medicine, Salt Lake City, UT 84132, USA. kristina.callis@hsc.utah.edu
Woodcock
Jamie
J
Krueger
Gerald G
GG
D015535:Arthritis, Psoriatic / Q000453:epidemiology / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000276:immunology; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D008297:Male; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology
D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; D053759:Interleukin-23; D023083:beta-Defensins; D018664:Interleukin-12