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Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BMJ Group
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002763/ https://www.ncbi.nlm.nih.gov/pubmed/20643763 http://dx.doi.org/10.1136/ard.2010.130575 |
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author | Bowes, John Flynn, Edward Ho, Pauline Aly, Batool Morgan, Ann W Marzo-Ortega, Helena Coates, Laura McManus, Ross Ryan, Anthony W Kane, David Korendowych, Eleanor McHugh, Neil FitzGerald, Oliver Packham, Jonathan Bruce, Ian N Barton, Anne |
author_facet | Bowes, John Flynn, Edward Ho, Pauline Aly, Batool Morgan, Ann W Marzo-Ortega, Helena Coates, Laura McManus, Ross Ryan, Anthony W Kane, David Korendowych, Eleanor McHugh, Neil FitzGerald, Oliver Packham, Jonathan Bruce, Ian N Barton, Anne |
author_sort | Bowes, John |
collection | PubMed |
description | 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 (p(trend) = 0.001, OR 1.19 and p(trend) = 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. |
format | Text |
id | pubmed-3002763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BMJ Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-30027632011-01-03 Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis Bowes, John Flynn, Edward Ho, Pauline Aly, Batool Morgan, Ann W Marzo-Ortega, Helena Coates, Laura McManus, Ross Ryan, Anthony W Kane, David Korendowych, Eleanor McHugh, Neil FitzGerald, Oliver Packham, Jonathan Bruce, Ian N Barton, Anne Ann Rheum Dis Basic and Translational Research 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 (p(trend) = 0.001, OR 1.19 and p(trend) = 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. BMJ Group 2010-09-21 /pmc/articles/PMC3002763/ /pubmed/20643763 http://dx.doi.org/10.1136/ard.2010.130575 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode. |
spellingShingle | Basic and Translational Research Bowes, John Flynn, Edward Ho, Pauline Aly, Batool Morgan, Ann W Marzo-Ortega, Helena Coates, Laura McManus, Ross Ryan, Anthony W Kane, David Korendowych, Eleanor McHugh, Neil FitzGerald, Oliver Packham, Jonathan Bruce, Ian N Barton, Anne Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis |
title | Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis |
title_full | Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis |
title_fullStr | Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis |
title_full_unstemmed | Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis |
title_short | Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis |
title_sort | variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis |
topic | Basic and Translational Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002763/ https://www.ncbi.nlm.nih.gov/pubmed/20643763 http://dx.doi.org/10.1136/ard.2010.130575 |
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