Risk variants for psoriasis vulgaris in a large case–control collection and association with clinical subphenotypes

Abstract

Recent genome-wide association studies (GWASs) have identified >20 new loci associated with the susceptibility to psoriasis vulgaris (PsV) risk. We investigated the association of PsV and its main clinical subphenotypes with 32 loci having previous genome-wide evidence of association with PsV (P < 5e-8) or strong GWAS evidence (P < 5e-5 in discovery and P < 0.05 in replication sample) in a large cohort of PsV patients (n = 2005) and controls (n = 1497). We provide the first independent replication for COG6 (P = 0.00079) and SERPINB8 (P = 0.048) loci with PsV. In those patients having developed psoriatic arthritis (n = 955), we found, for the first time, a strong association with IFIH1 (P = 0.013). Analyses of clinically relevant PsV subtypes yielded a significant association of severity of cutaneous disease with variation at LCE3D locus (P = 0.0005) in PsV and nail involvement with IL1RN in purely cutaneous psoriasis (PsC, P = 0.007). In an exploratory analysis of epistasis, we replicated the previously described HLA-C-ERAP1 interaction with PsC. Our findings show that common genetic variants associated with a complex phenotype like PsV influence different subphenotypes of high clinical relevance.

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

“…There is a strong association of the LCE3D locus with severity of Ps. The ratio of individuals carrying two copies of the risk allele was about 25% higher in the moderate-to-severe group than in the mild disease group (45.8% vs 37%), supporting the role of LCE3D allele in the development of more severe forms of Ps (Julia et al, 2012). Significant association between the severity of Ps and the variation at LCE3D locus indicates that LCE3D influences the Ps subphenotypes.…”

Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis

“…The patients were recruited from the outpatients clinics of the dermatology departments from 11 university hospitals from Spain participating in the IMID Consortium. 15 Psoriasis patients with plaque psoriasis affecting torso and/or extremities and with at least 1 year of duration were included. Patients with a single clinical localization of plaque psoriasis (i.e.…”

“…14 Genetic variation not only contributes to the increased risk of developing psoriasis but it has also been shown to influence the risk of developing different clinically relevant phenotypes. 15 Using this approach, psoriasis risk locus TNFAIP3 (refs 2,5) locus has been recently found to be associated with the response to anti-TNF therapy. 16 In particular, it was found that the association was significant in the patients treated with etanercept, a TNF receptor fusion protein, but not with anti-TNF monoclonal antibodies adalimumab and infliximab.…”

Genetic, Epigenetic and Pharmacogenetic Aspects of Psoriasis and Psoriatic Arthritis

“…79 Although GWAS studies in psoriasis failed to detect an association with IL-1b, 22-33 IL-1RN was associated significantly with cutaneous disease severity and nail involvement in purely cutaneous psoriasis. 80 Although the IL-1 locus was initially considered a PsA susceptibility locus, 81,82 this finding was not confirmed in follow-up studies. [27][28][29]83 IL-23 is a heterodimeric cytokine that binds IL-23R and IL-12Rb1, promotes the expansion and survival of Th-17 cells, 83,84 and acts as a proinflammatory mediator.…”