A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma PPAR-γ gene and systemic sclerosisReport as inadecuate




A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma PPAR-γ gene and systemic sclerosis - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Northwestern University 2 Institut Cochin 3 Rheumatology Department, Cochin Hospital, Rheumatology Department 4 U699 5 Université de Lille, Droit et Santé 6 CHU Saint-Antoine APHP 7 CIC - Grenoble

Abstract : 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.





Author: Roberta Goncalves Marangoni - Benjamin D. Korman - Yannick Allanore - Philippe Dieude - Loren L. Armstrong - Margarita Rzhetskaya

Source: https://hal.archives-ouvertes.fr/



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