Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis

Elisa Docampo, Raquel Rabionet, Eva Riveira-Muñoz, Georgia Escaramís, Antonio Julià, Sara Marsal, José Ezequiel Martín, Miguel Angel González-Gay, Alejandro Balsa, Enrique Raya, Javier Martín, Xavier P. Estivill

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Objective. The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA. Methods. We tested for association between the LCE3C-LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case-control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C-LCE3B deletion (LCE3C-LCE3B-del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package. Results. An association of homozygosity for the LCE3C-LCE3B-del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case-control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.16-1.81) for association of the LCE3C-LCE3B-del. When the analysis was stratified for serologic data, we observed association in anti-cyclic citrullinated peptide (anti-CCP)-positive patients (P = 0.012, OR 1.51 [95% CI 1.09-2.13]) but not in anti-CCP-negative patients. Conclusion. We have identified an association between the LCE3C-LCE3B-del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C-LCE3B-del) for autoimmune diseases that is involved in both psoriasis and RA.

Original languageEnglish
Pages (from-to)1246-1251
Number of pages6
JournalArthritis and Rheumatism
Volume62
Issue number5
DOIs
Publication statusPublished - May 2010
Externally publishedYes

Fingerprint

Rheumatoid Arthritis
Genes
Psoriasis
Gene Deletion
Odds Ratio
Confidence Intervals
Linkage Disequilibrium
Multigene Family
Autoimmune Diseases
Single Nucleotide Polymorphism
Alleles
Polymerase Chain Reaction
Population

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis. / Docampo, Elisa; Rabionet, Raquel; Riveira-Muñoz, Eva; Escaramís, Georgia; Julià, Antonio; Marsal, Sara; Martín, José Ezequiel; González-Gay, Miguel Angel; Balsa, Alejandro; Raya, Enrique; Martín, Javier; Estivill, Xavier P.

In: Arthritis and Rheumatism, Vol. 62, No. 5, 05.2010, p. 1246-1251.

Research output: Contribution to journalArticle

Docampo, E, Rabionet, R, Riveira-Muñoz, E, Escaramís, G, Julià, A, Marsal, S, Martín, JE, González-Gay, MA, Balsa, A, Raya, E, Martín, J & Estivill, XP 2010, 'Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis', Arthritis and Rheumatism, vol. 62, no. 5, pp. 1246-1251. https://doi.org/10.1002/art.27381
Docampo E, Rabionet R, Riveira-Muñoz E, Escaramís G, Julià A, Marsal S et al. Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis. Arthritis and Rheumatism. 2010 May;62(5):1246-1251. https://doi.org/10.1002/art.27381
Docampo, Elisa ; Rabionet, Raquel ; Riveira-Muñoz, Eva ; Escaramís, Georgia ; Julià, Antonio ; Marsal, Sara ; Martín, José Ezequiel ; González-Gay, Miguel Angel ; Balsa, Alejandro ; Raya, Enrique ; Martín, Javier ; Estivill, Xavier P. / Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 5. pp. 1246-1251.
@article{03e5154878dc471e93f57ac990f8a41b,
title = "Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis",
abstract = "Objective. The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA. Methods. We tested for association between the LCE3C-LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case-control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C-LCE3B deletion (LCE3C-LCE3B-del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package. Results. An association of homozygosity for the LCE3C-LCE3B-del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case-control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95{\%} confidence interval [95{\%} CI] 1.16-1.81) for association of the LCE3C-LCE3B-del. When the analysis was stratified for serologic data, we observed association in anti-cyclic citrullinated peptide (anti-CCP)-positive patients (P = 0.012, OR 1.51 [95{\%} CI 1.09-2.13]) but not in anti-CCP-negative patients. Conclusion. We have identified an association between the LCE3C-LCE3B-del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C-LCE3B-del) for autoimmune diseases that is involved in both psoriasis and RA.",
author = "Elisa Docampo and Raquel Rabionet and Eva Riveira-Mu{\~n}oz and Georgia Escaram{\'i}s and Antonio Juli{\`a} and Sara Marsal and Mart{\'i}n, {Jos{\'e} Ezequiel} and Gonz{\'a}lez-Gay, {Miguel Angel} and Alejandro Balsa and Enrique Raya and Javier Mart{\'i}n and Estivill, {Xavier P.}",
year = "2010",
month = "5",
doi = "10.1002/art.27381",
language = "English",
volume = "62",
pages = "1246--1251",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis

AU - Docampo, Elisa

AU - Rabionet, Raquel

AU - Riveira-Muñoz, Eva

AU - Escaramís, Georgia

AU - Julià, Antonio

AU - Marsal, Sara

AU - Martín, José Ezequiel

AU - González-Gay, Miguel Angel

AU - Balsa, Alejandro

AU - Raya, Enrique

AU - Martín, Javier

AU - Estivill, Xavier P.

PY - 2010/5

Y1 - 2010/5

N2 - Objective. The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA. Methods. We tested for association between the LCE3C-LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case-control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C-LCE3B deletion (LCE3C-LCE3B-del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package. Results. An association of homozygosity for the LCE3C-LCE3B-del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case-control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.16-1.81) for association of the LCE3C-LCE3B-del. When the analysis was stratified for serologic data, we observed association in anti-cyclic citrullinated peptide (anti-CCP)-positive patients (P = 0.012, OR 1.51 [95% CI 1.09-2.13]) but not in anti-CCP-negative patients. Conclusion. We have identified an association between the LCE3C-LCE3B-del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C-LCE3B-del) for autoimmune diseases that is involved in both psoriasis and RA.

AB - Objective. The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA. Methods. We tested for association between the LCE3C-LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case-control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C-LCE3B deletion (LCE3C-LCE3B-del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package. Results. An association of homozygosity for the LCE3C-LCE3B-del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case-control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.16-1.81) for association of the LCE3C-LCE3B-del. When the analysis was stratified for serologic data, we observed association in anti-cyclic citrullinated peptide (anti-CCP)-positive patients (P = 0.012, OR 1.51 [95% CI 1.09-2.13]) but not in anti-CCP-negative patients. Conclusion. We have identified an association between the LCE3C-LCE3B-del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C-LCE3B-del) for autoimmune diseases that is involved in both psoriasis and RA.

UR - http://www.scopus.com/inward/record.url?scp=77951750868&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951750868&partnerID=8YFLogxK

U2 - 10.1002/art.27381

DO - 10.1002/art.27381

M3 - Article

VL - 62

SP - 1246

EP - 1251

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 5

ER -