title: Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis.
abstract: Psoriasis is a prevalent autoimmune disease of the skin that causes significant psychological and physical disability. Tumor necrosis factor (TNF)-blocking agents have proven to be highly efficacious in the management of moderate-to-severe psoriasis. However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly associated with anti-TNF response in rheumatoid arthritis. Using a cohort of 130 psoriasis patients treated with anti-TNF therapy, we sought to analyze the association of this locus with treatment response in psoriasis. We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (P=0.0031). Importantly, the allele that was previously associated with the lack of response to rheumatoid arthritis (G allele, single-nucleotide polymorphism rs3794271) was associated with a higher anti-TNF efficacy in psoriasis. The results of this study are an important step in the characterization of the pharmacogenetic profile associated with anti-TNF response in psoriasis.
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Julià
authors.affiliation: Dermatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Ferrándiz
authors.affiliation: Dermatology Department, Hospital Universitario La Princesa, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Dauden
authors.affiliation: Dermatology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain.
authors.forename: E
authors.identifier: 0000000280482681
authors.initials: E
authors.lastname: Fonseca
authors.affiliation: Dermatology Department, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Fernández-López
authors.affiliation: Dermatology Department, Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Sanchez-Carazo
authors.affiliation: Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Vanaclocha
authors.affiliation: Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: L
authors.identifier: 0000000160830952
authors.initials: L
authors.lastname: Puig
authors.affiliation: Dermatology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Moreno-Ramírez
authors.affiliation: Dermatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Lopez-Estebaranz
authors.affiliation: Dermatology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Herrera
authors.affiliation: Dermatology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: de la Cueva
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Ávila
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Tortosa
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López-Lasanta
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Marsal
mesh_terms: D000328:Adult; D000483:Alleles; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics; D015331:Cohort Studies; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics*; D023381:Endpoint Determination; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D027361:Organic Anion Transporters; C473187:SLCO1C1 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517287:PDE3A protein, human