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Extended report
Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis
  1. John Bowes1,
  2. Edward Flynn1,
  3. Pauline Ho1,2,
  4. Batool Aly1,
  5. Ann W Morgan3,
  6. Helena Marzo-Ortega3,
  7. Laura Coates3,
  8. Ross McManus4,
  9. Anthony W Ryan4,
  10. David Kane5,
  11. Eleanor Korendowych6,7,
  12. Neil McHugh6,7,
  13. Oliver FitzGerald8,
  14. Jonathan Packham9,
  15. Ian N Bruce1,2,
  16. Anne Barton1,2
  1. 1Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  2. 2The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester, UK
  3. 3NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
  4. 4Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
  5. 5Adelaide and Meath Hospital and Trinity College Dublin, Dublin, UK
  6. 6Royal National Hospital for Rheumatic Diseases, Bath, UK
  7. 7Department Pharmacy and Pharmacology, University of Bath, Bath, UK
  8. 8Department of Rheumatology, St Vincent's University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
  9. 9Arthritis Research Campaign National Primary Care Centre, Keele University, Stoke on Trent, UK
  1. Correspondence to Dr Anne Barton, Arthritis Research UK Epidemiology Unit, Stopford Building, Oxford Road, University of Manchester, Manchester M13 9PT, UK; anne.barton{at}


Objective A common deletion mapping to the psoriasis susceptibility locus 4 on chromosome 1q21, encompassing two genes of the late cornified envelope (LCE) gene cluster, has been associated with an increased risk of psoriasis vulgaris (PsV). One previous report found no association of the deletion with psoriatic arthritis (PsA), suggesting it may be a specific risk factor for PsV. Given the genetic overlap between PsA and PsV, a study was undertaken to investigate whether single nucleotide polymorphisms (SNPs) mapping to this locus are risk factors for PsA in a UK and Irish population.

Methods Three SNPs with prior evidence of association with susceptibility to PsV were genotyped in 1057 patients with PsA using Sequenom iPlex chemistry and genotype frequencies compared with data available for 5575 healthy controls. Two of the SNPs, rs4112788 and rs4085613, were reported to be highly correlated with the LCE deletion. The third SNP, rs6701216, was previously reported to be associated with PsV in a US population.

Results Alleles tagging the deletion for both rs4112788 and rs4085613 were found to be enriched in cases compared with controls (69% vs 65%) and significantly associated with increased susceptibility to PsA (ptrend = 0.001, OR 1.19 and ptrend = 0.001, OR 1.18, respectively). No association was observed with rs6701216.

Conclusions The evidence presented here supports LCE deletion as a risk factor for PsA in a UK and Irish population. It suggests that this locus is a risk factor within a shared aetiological pathway that contributes to psoriatic skin disease in both PsV and PsA.

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  • Funding JB, INB and AB are funded by Arthritis Research UK (arc grant 17552). EF is supported by the European Community's Sixth Framework Programme AutoCure funding. Funding for the project was provided by the Wellcome Trust under award 076113 and 085475. This work was funded by the Arthritis Research UK.

  • Ethics approval This study was conducted with the approval of the Central Manchester Research Ethics Committee MREC 99/8/84 and all subjects provided informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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