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 TievLuc Letenneur, Philippe Amouyel, Jean Charles Lambert, Gilles Chiocchia, Maria Martinez, Lidia Ibba-Manneschi, Marco Matucci-Cerinic

Research output: Contribution to journalArticlepeer-review


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
Issue number6
Publication statusPublished - Jun 2012

ASJC Scopus subject areas

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


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