title: Deletion of LCE3C and LCE3B is a susceptibility factor for psoriatic arthritis: a study in Spanish and Italian populations and meta-analysis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Genomic Regulation-Pompeu Fabra University and Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Docampo
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
authors.forename: Eva
authors.initials: E
authors.lastname: Riveira-Muñoz
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Georgia
authors.initials: G
authors.lastname: Escaramís
authors.forename: Carlo
authors.initials: C
authors.lastname: Perricone
authors.forename: José L
authors.initials: JL
authors.lastname: Fernández-Sueiro
authors.forename: Joan
authors.initials: J
authors.lastname: Maymó
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hüffmeier
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Lisbona
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Raquel
authors.initials: R
authors.lastname: Rabionet
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000328:Adult; D000483:Alleles; D015535:Arthritis, Psoriatic / Q000235:genetics*; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D044465:White People / Q000235:genetics
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; C549748:LCE3B protein, human; C524768:LCE3C protein, human