Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis

Mirko Manetti, Yannick Allanore, Mohamad Saad, Cinzia Fatini, Vanessa Cohignac, Serena Guiducci, Eloisa Romano, Paolo Airó, Paola Caramaschi, Ilaria Tinazzi, Valeria Riccieri, Alessandra Della Rossa, Rosanna Abbate, Roberto Caporali, Giovanna Cuomo, Guido Valesini, Philippe Dieudé, Eric Hachulla, Jean Luc Cracowski, Kiet Tiev & 7 others Luc Letenneur, Philippe Amouyel, Jean Charles Lambert, Gilles Chiocchia, Maria Martinez, Lidia Ibba-Manneschi, Marco Matucci-Cerinic

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objective: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc. Methods: A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most signifi cant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting. Results: In the French population, the CAV1 rs959173 C minor allele showed a signifi cant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p adjusted=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p adjusted=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel metaanalysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression. Conclusions: These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.

Original languageEnglish
Pages (from-to)1034-1041
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume71
Issue number6
DOIs
Publication statusPublished - 1 Jun 2012
Externally publishedYes

Fingerprint

Caveolin 1
Systemic Scleroderma
Fibrosis
Genes
Tissue
Polymorphism
Nucleotides
Population
Caveolins
Single Nucleotide Polymorphism
Skin
Proteins
Biopsy
Alleles
Genotype

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis. / Manetti, Mirko; Allanore, Yannick; Saad, Mohamad; Fatini, Cinzia; Cohignac, Vanessa; Guiducci, Serena; Romano, Eloisa; Airó, Paolo; Caramaschi, Paola; Tinazzi, Ilaria; Riccieri, Valeria; Della Rossa, Alessandra; Abbate, Rosanna; Caporali, Roberto; Cuomo, Giovanna; Valesini, Guido; Dieudé, Philippe; Hachulla, Eric; Cracowski, Jean Luc; Tiev, Kiet; Letenneur, Luc; Amouyel, Philippe; Lambert, Jean Charles; Chiocchia, Gilles; Martinez, Maria; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco.

In: Annals of the Rheumatic Diseases, Vol. 71, No. 6, 01.06.2012, p. 1034-1041.

Research output: Contribution to journalArticle

Manetti, M, Allanore, Y, Saad, M, Fatini, C, Cohignac, V, Guiducci, S, Romano, E, Airó, P, Caramaschi, P, Tinazzi, I, Riccieri, V, Della Rossa, A, Abbate, R, Caporali, R, Cuomo, G, Valesini, G, Dieudé, P, Hachulla, E, Cracowski, JL, Tiev, K, Letenneur, L, Amouyel, P, Lambert, JC, Chiocchia, G, Martinez, M, Ibba-Manneschi, L & Matucci-Cerinic, M 2012, 'Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis', Annals of the Rheumatic Diseases, vol. 71, no. 6, pp. 1034-1041. https://doi.org/10.1136/annrheumdis-2011-200986
Manetti, Mirko ; Allanore, Yannick ; Saad, Mohamad ; Fatini, Cinzia ; Cohignac, Vanessa ; Guiducci, Serena ; Romano, Eloisa ; Airó, Paolo ; Caramaschi, Paola ; Tinazzi, Ilaria ; Riccieri, Valeria ; Della Rossa, Alessandra ; Abbate, Rosanna ; Caporali, Roberto ; Cuomo, Giovanna ; Valesini, Guido ; Dieudé, Philippe ; Hachulla, Eric ; Cracowski, Jean Luc ; Tiev, Kiet ; Letenneur, Luc ; Amouyel, Philippe ; Lambert, Jean Charles ; Chiocchia, Gilles ; Martinez, Maria ; Ibba-Manneschi, Lidia ; Matucci-Cerinic, Marco. / Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis. In: Annals of the Rheumatic Diseases. 2012 ; Vol. 71, No. 6. pp. 1034-1041.
@article{1a362c8b78bd49d4bd8e2a75dd790996,
title = "Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis",
abstract = "Objective: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc. Methods: A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most signifi cant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting. Results: In the French population, the CAV1 rs959173 C minor allele showed a signifi cant protective association with susceptibility to SSc (OR 0.71, 95{\%} CI 0.59 to 0.86, p adjusted=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95{\%} CI 0.56 to 0.89, p adjusted=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel metaanalysis (SSc: pooled OR 0.81, 95{\%} CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95{\%} CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression. Conclusions: These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.",
author = "Mirko Manetti and Yannick Allanore and Mohamad Saad and Cinzia Fatini and Vanessa Cohignac and Serena Guiducci and Eloisa Romano and Paolo Air{\'o} and Paola Caramaschi and Ilaria Tinazzi and Valeria Riccieri and {Della Rossa}, Alessandra and Rosanna Abbate and Roberto Caporali and Giovanna Cuomo and Guido Valesini and Philippe Dieud{\'e} and Eric Hachulla and Cracowski, {Jean Luc} and Kiet Tiev and Luc Letenneur and Philippe Amouyel and Lambert, {Jean Charles} and Gilles Chiocchia and Maria Martinez and Lidia Ibba-Manneschi and Marco Matucci-Cerinic",
year = "2012",
month = "6",
day = "1",
doi = "10.1136/annrheumdis-2011-200986",
language = "English",
volume = "71",
pages = "1034--1041",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "6",

}

TY - JOUR

T1 - Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis

AU - Manetti, Mirko

AU - Allanore, Yannick

AU - Saad, Mohamad

AU - Fatini, Cinzia

AU - Cohignac, Vanessa

AU - Guiducci, Serena

AU - Romano, Eloisa

AU - Airó, Paolo

AU - Caramaschi, Paola

AU - Tinazzi, Ilaria

AU - Riccieri, Valeria

AU - Della Rossa, Alessandra

AU - Abbate, Rosanna

AU - Caporali, Roberto

AU - Cuomo, Giovanna

AU - Valesini, Guido

AU - Dieudé, Philippe

AU - Hachulla, Eric

AU - Cracowski, Jean Luc

AU - Tiev, Kiet

AU - Letenneur, Luc

AU - Amouyel, Philippe

AU - Lambert, Jean Charles

AU - Chiocchia, Gilles

AU - Martinez, Maria

AU - Ibba-Manneschi, Lidia

AU - Matucci-Cerinic, Marco

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Objective: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc. Methods: A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most signifi cant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting. Results: In the French population, the CAV1 rs959173 C minor allele showed a signifi cant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p adjusted=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p adjusted=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel metaanalysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression. Conclusions: These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.

AB - Objective: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc. Methods: A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most signifi cant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting. Results: In the French population, the CAV1 rs959173 C minor allele showed a signifi cant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p adjusted=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p adjusted=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel metaanalysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression. Conclusions: These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84860916453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860916453&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2011-200986

DO - 10.1136/annrheumdis-2011-200986

M3 - Article

VL - 71

SP - 1034

EP - 1041

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 6

ER -