A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis.
Arthritis Res Ther
; 17: 128, 2015 May 19.
Article
en En
| MEDLINE
| ID: mdl-25986483
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esclerodermia Sistémica
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ARN
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Regulación de la Expresión Génica
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Predisposición Genética a la Enfermedad
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Receptores Activados del Proliferador del Peroxisoma
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PPAR gamma
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Arthritis Res Ther
Asunto de la revista:
REUMATOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos