Deletion of LCE3C and LCE3B is a susceptibility factor for psoriatic arthritis: a study in Spanish and Italian populations and meta-analysis

Arthritis Rheum. 2011 Jul;63(7):1860-5. doi: 10.1002/art.30340.

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.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Arthritis, Psoriatic / genetics*
  • Cornified Envelope Proline-Rich Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Spain
  • White People / genetics

Substances

  • Cornified Envelope Proline-Rich Proteins
  • LCE3B protein, human
  • LCE3C protein, human