• 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, and M Geoffrey Hayes.
• Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 E. Huron Street, McGaw Pavillion M230, Chicago, IL, USA. roberta.marangoni@northwestern.edu.
• Arthritis Res. Ther. 2015 May 19; 17: 128.

IntroductionThe 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.MethodsTag 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.ResultsIn 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).ConclusionsA PPARG variant is associated with susceptibility to SSc, consistent with a role of PPAR-γ in the pathogenesis of SSc.

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