A replication study of the association between rheumatoid arthritis and deletion of the late cornified envelope genes LCE3B and LCE3C

PLoS One. 2012;7(2):e32045. doi: 10.1371/journal.pone.0032045. Epub 2012 Feb 23.


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).

Conclusion: 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.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / metabolism*
  • Autoimmunity / genetics
  • China
  • Cohort Studies
  • Cornified Envelope Proline-Rich Proteins / metabolism*
  • Female
  • Gene Deletion*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Peptides / chemistry
  • Psoriasis
  • Risk
  • Risk Factors
  • Spain


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