학술논문
A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility
Document Type
Report
Author
López-Isac, Elena; Bossini-Castillo, Lara; Simeon, Carmen P; Egurbide, María Victoria; Alegre-Sancho, Juan Josñ; Callejas, Jose Luis; Roman-Ivorra, Josñ Andrñs; 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; Vonk, Madelon C; Voskuyl, Alexandre E; Shiels, Paul G; van Laar, Jacob M; Fonseca, Carmen; Denton, Christopher; Herrick, Ariane; Worthington, Jane; Assassi, Shervin; Koeleman, Bobby P; Mayes, Maureen D; Radstake, Timothy RDJ; Martin, Javier
Source
Arthritis Research & Therapy. January 9, 2014, Vol. 16
Subject
Language
English
ISSN
1478-6354
Abstract
Author(s): Elena López-Isac[sup.1] , Lara Bossini-Castillo[sup.1] , Carmen P Simeon[sup.2] , María Victoria Egurbide[sup.3] , Juan Josñ Alegre-Sancho[sup.4] , Jose Luis Callejas[sup.5] , Josñ Andrñs Roman-Ivorra[sup.6] , Mayka Freire[sup.7] , [...]
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 Results We observed nominal associations for both PPARG rs310746 (P.sub.MH = 1.90 x 10.sup.-6, OR, 1.28) and CHRNA9 rs6832151 (P.sub.MH = 4.30 x 10.sup.-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 (P.sub.MH = 5.00 x 10.sup.-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.
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 Results We observed nominal associations for both PPARG rs310746 (P.sub.MH = 1.90 x 10.sup.-6, OR, 1.28) and CHRNA9 rs6832151 (P.sub.MH = 4.30 x 10.sup.-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 (P.sub.MH = 5.00 x 10.sup.-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.