A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis

Roberta Goncalves Marangoni*, Benjamin D. Korman, Yannick Allanore, Philippe Dieude, Loren L. Armstrong, Margarita Rzhetskaya, Monique Hinchcliff, Mary Carns, Sofia Podlusky, Sanjiv J. Shah, Barbara Ruiz, Eric Hachulla, Kiet Tiev, Jean Luc Cracowski, John Varga, M. Geoffrey Hayes

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Introduction: The multifunctional nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) has potent anti-fibrotic effects, and its expression and activity are impaired in patients with systemic sclerosis (SSc). We investigated PPAR-γ gene (PPARG) single nucleotide polymorphisms (SNPs) associated with SSc. Methods: Tag SNPs spanning PPARG were genotyped in a European ancestry US discovery cohort comprising 152 SSc patients and 450 controls, with replication of our top signal in a European cohort (1031 SSc patients and 1014 controls from France). Clinical parameters and disease severity were analyzed to evaluate clinical associations with PPARG variants. Results: In the discovery cohort, a single PPARG intronic SNP (rs10865710) was associated with SSc (p = 0.010; odds ratio = 1.52 per C allele, 95% confidence interval 1.10-2.08). This association was replicated in the French validation cohort (p = 0.052; odds ratio = 1.16 per C allele, 95% confidence interval 1.00-1.35). Meta-analysis of both cohorts indicated stronger evidence for association (p = 0.002; odds ratio = 1.22 per C allele, 95% confidence interval 1.07-1.40). The rs10865710 C allele was also associated with pulmonary arterial hypertension in the French SSc cohort (p = 0.002; odds ratio = 2.33 per C allele, 95% confidence interval 1.34-4.03). Conclusions: A PPARG variant is associated with susceptibility to SSc, consistent with a role of PPAR-γ in the pathogenesis of SSc.

Original languageEnglish (US)
Article number128
JournalArthritis Research and Therapy
Volume17
Issue number1
DOIs
StatePublished - May 19 2015

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Marangoni, R. G., Korman, B. D., Allanore, Y., Dieude, P., Armstrong, L. L., Rzhetskaya, M., Hinchcliff, M., Carns, M., Podlusky, S., Shah, S. J., Ruiz, B., Hachulla, E., Tiev, K., Cracowski, J. L., Varga, J., & Hayes, M. G. (2015). A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis. Arthritis Research and Therapy, 17(1), [128]. https://doi.org/10.1186/s13075-015-0641-2