Title |
A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis
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Published in |
Arthritis Research & Therapy, May 2015
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DOI | 10.1186/s13075-015-0641-2 |
Pubmed ID | |
Authors |
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 |
Abstract |
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. 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. 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). A PPARG variant is associated with susceptibility to SSc, consistent with a role of PPAR-γ in the pathogenesis of SSc. |
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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 31 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 4 | 13% |
Student > Ph. D. Student | 3 | 10% |
Student > Bachelor | 3 | 10% |
Student > Postgraduate | 3 | 10% |
Professor > Associate Professor | 3 | 10% |
Other | 8 | 26% |
Unknown | 7 | 23% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 9 | 29% |
Biochemistry, Genetics and Molecular Biology | 3 | 10% |
Immunology and Microbiology | 3 | 10% |
Agricultural and Biological Sciences | 2 | 6% |
Unspecified | 1 | 3% |
Other | 1 | 3% |
Unknown | 12 | 39% |