title: A replication study of the association between rheumatoid arthritis and deletion of the late cornified envelope genes LCE3B and LCE3C.
abstract: OBJECTIVE
  Two recent studies, in a Spanish and a Chinese population, point to an association between rheumatoid arthritis (RA) risk and the deletion of the Late Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor for psoriasis. We aimed to replicate these studies in a large Dutch cohort.
  
  
  METHODS
  1039 RA cases and 759 controls were genotyped for LCE3C_LCE3B-del. Association analysis was performed for the complete cohort and after stratification for the serologic markers anti-cyclic citrullinated peptide and rheumatoid factor. A meta-analysis was performed combining our data with the Spanish and Chinese datasets, resulting in an analysis including 2466 RA cases and 2438 controls.
  
  
  RESULTS
  In the Dutch cohort we did not observe a significant association of LCE3C_LCE3B-del (p = 0.093) with RA risk. A stratified analysis for the serologic positive and negative group did not show an association between the genetic variant and disease risk, either. The meta-analysis, however, confirmed a significant association (p<0.0001, OR = 1.31, 95% confidence interval 1.16-1.47).
  
  
  CONCLUSIONS
  Our meta-analysis confirms the association of the LCE3 deletion with RA, suggesting that LCE3C_LCE3B-del is a common risk factor for (auto)immune diseases.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Judith G M
authors.initials: JG
authors.lastname: Bergboer
authors.forename: Maša
authors.initials: M
authors.lastname: Umićević-Mirkov
authors.forename: Jaap
authors.initials: J
authors.lastname: Fransen
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015551:Autoimmunity / Q000235:genetics; D002681:China; D015331:Cohort Studies; D055233:Cornified Envelope Proline-Rich Proteins / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010455:Peptides / Q000737:chemistry; D011565:Psoriasis; D012306:Risk; D012307:Risk Factors; D013030:Spain
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; C549748:LCE3B protein, human; C524768:LCE3C protein, human; D010455:Peptides