6533b7d7fe1ef96bd12685f0

RESEARCH PRODUCT

Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study

Paloma García De La PeñaMiguel A. Gonzalez-gayPatricia CarreiraTimothy R D J RadstakeTimothy R D J RadstakeGerard EspinosaLara Bossini-castilloAlexandre E. VoskuylRoger HesselstrandNatividad OreiroCarmen FonsecaChristopher P. DentonIvan CastellvíAnna Maria Hoffmann-voldLuis Sáez-cometShervin AssassiAnnemie J. SchuerweghJane WorthingtonPaul G. ShielsMaureen D. MayesAriane L. HerrickM.j. CastilloJacob M Van LaarFilemon K. TanJose Ezequiel MartinAnnika NordinNorberto Ortego-centenoOlga Y. GorlovaRaffaella ScorzaBobby P. C. KoelemanJasper C A BroenJosé Andrés Román-ivorraClaudio LunardiLorenzo BerettaFrank C. ArnettCarmen P. SimeonMadelon C. VonkJavier Martín

subject

Oncologymedicine.medical_specialtysystemic sclerosisRHOBImmunologyGenome-wide association studySingle-nucleotide polymorphismBioinformaticsPolymorphism Single NucleotideGeneral Biochemistry Genetics and Molecular BiologyArticleWhite PeopleRheumatologyRisk FactorsInternal medicineRhoB GTP-Binding Proteinsystemic sclerosis; genome wide screening; genetic risk factorsmedicinegenetic risk factorsImmunology and AllergySNPHumansGenetic Predisposition to DiseaseAllelerhoB GTP-Binding ProteinRheumatology and AutoimmunityScleroderma Systemicbusiness.industryHaplotypeProteinsgenome wide screeningDNA-Binding ProteinsEuropeHaplotypesCohortEvaluation of complex medical interventions Auto-immunity transplantation and immunotherapy [NCEBP 2]businessGenome-Wide Association Study

description

Item does not contain fulltext INTRODUCTION: A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. METHODS: 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. RESULTS: Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 p(MH)=1.94x10(-4), OR 1.19; rs4958881 p(MH)=3.26x10(-5), OR 1.19; rs3792783 p(MH)=2.16x10(-4), OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. CONCLUSIONS: These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor.

yearjournalcountryeditionlanguage
2012-08-15
http://lup.lub.lu.se/record/3669874