Docampo, Elisa, Giardina, Emiliano, Riveira-Muñoz, Eva, de Cid, Rafael, Escaramís, Georgia, Perricone, Carlo, Fernández-Sueiro, José L., Maymó, Joan, González-Gay, Miguel A., Blanco, Francisco J., Hüffmeier, Ulrike, Lisbona, M. Pilar, Martín, Javier, Carracedo, Ángel, Reis, André, Rabionet, Raquel, Novelli, Giuseppe, and Estivill, Xavier
Objective The LCE3C_LCE3B-del variant is associated with psoriasis and rheumatoid arthritis. Its role in psoriatic arthritis (PsA) is unclear, however, as shown by 3 recent studies with contradictory results. In order to investigate whether LCE3C_LCE3B-del constitutes a risk factor for PsA susceptibility, we first tested this variant in patients with PsA from Spanish and Italian populations and then performed a meta-analysis including the previous case-control studies. Methods We genotyped LCE3C_LCE3B-del and its tag single-nucleotide polymorphism (SNP), rs4112788, in an original discovery cohort of 424 Italian patients with PsA and 450 unaffected control subjects. A Spanish replication cohort consisting of 225 patients with PsA and 469 control subjects was also genotyped. A meta-analysis considering 7,758 control subjects and 2,325 patients with PsA was also performed. Results We observed a significant association between PsA and the LCE3C_LCE3B-del tag SNP in the Italian and Spanish cohorts, with an overall corrected P value of 0.00019 and a corresponding odds ratio of 1.35 (95% confidence interval 1.14-1.59). Stratified analyses by subphenotype indicated a stronger association for patients with oligoarticular disease. Meta-analysis including data from all previous published studies confirmed an association of PsA with the LCE3C_LCE3B-del tag SNP. Conclusion LCE3C_LCE3B-del is a susceptibility factor for PsA, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders. [ABSTRACT FROM AUTHOR]