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

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 (...

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Detalles Bibliográficos
Autores principales: Marangoni, Roberta Goncalves, Korman, Benjamin D, Allanore, Yannick, Dieude, Philippe, Armstrong, Loren L, Rzhetskaya, Margarita, Hinchcliff, Monique, Carns, Mary, Podlusky, Sofia, Shah, Sanjiv J, Ruiz, Barbara, Hachulla, Eric, Tiev, Kiet, Cracowski, Jean-Luc, Varga, John, Hayes, M Geoffrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437446/
https://www.ncbi.nlm.nih.gov/pubmed/25986483
http://dx.doi.org/10.1186/s13075-015-0641-2
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-015-0641-2) contains supplementary material, which is available to authorized users.