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A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Abstract: INTRODUCTION: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy. METHODS: Sixty-six non-HLA SNPs showing a P value <10?4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. RESULTS: We observed nominal associations for both PPARG rs310746 (PMH?=?1.90?×?10?6, OR, 1.28) and CHRNA9 rs6832151 (PMH?=?4.30?×?10?6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value?=?0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH?=?5.00?×?10?7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis. CONCLUSION: Our results suggest a role of PPARG gene in the development of SSc.

 Fuente: Arthritis Research & Therapy, 2014,16, R6

 Editorial: BioMed Central

 Año de publicación: 2014

 Nº de páginas: 8

 Tipo de publicación: Artículo de Revista

 DOI: 10.1186/ar4432

 ISSN: 1478-6354,1478-6362

 Proyecto español: SAF2009-11110 ; SAF2012-34435 ; P09-CTS-4977 ; CTS-180

Autoría

LÓPEZ ISAC, ELENA

BOSSINI CASTILLO, LARA

SIMEON, CARMEN P.

EGURBIDE, MARÍA VICTORIA

ALEGRE SANCHO, JUAN JOSÉ

CALLEJAS, JOSE LUIS

ROMAN IVORRA, JOSÉ ANDRÉS

FREIRE, MAYKA

BERETTA, LORENZO

SANTANIELLO, ALESSANDRO

AIRÓ, PAOLO

LUNARDI, CLAUDIO

HUNZELMANN, NICOLAS

RIEMEKASTEN, GABRIELA

WITTE, TORSTEN

KREUTER, ALEXANDER

DISTLER, JÖRG H. W.

SCHUERWEGH, ANNEMIE J.