TY - JOUR
T1 - Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study
AU - Bossini-Castillo, Lara
AU - Martin, Jose Ezequiel
AU - Broen, Jasper
AU - Simeon, Carmen P.
AU - Beretta, Lorenzo
AU - Gorlova, Olga Y.
AU - Vonk, Madelon C.
AU - Ortego-Centeno, Norberto
AU - Espinosa, Gerard
AU - Carreira, Patricia
AU - De La Peña, Paloma García
AU - Oreiro, Natividad
AU - Román-Ivorra, José Andrés
AU - Castillo, María Jesús
AU - González-Gay, Miguel A.
AU - Sáez-Comet, Luis
AU - Castellví, Ivan
AU - Schuerwegh, Annemie J.
AU - Voskuyl, Alexandre E.
AU - Hoffmann-Vold, Anna Maria
AU - Hesselstrand, Roger
AU - Nordin, Annika
AU - Lunardi, Claudio
AU - Scorza, Raffaella
AU - Van Laar, Jacob M.
AU - Shiels, Paul G.
AU - Herrick, Ariane
AU - Worthington, Jane
AU - Fonseca, Carmen
AU - Denton, Christopher
AU - Tan, Filemon K.
AU - Arnett, Frank C.
AU - Assassi, Shervin
AU - Koeleman, Bobby P.
AU - Mayes, Maureen D.
AU - Radstake, Timothy R D J
AU - Martin, Javier
PY - 2013/4
Y1 - 2013/4
N2 - 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 pMH=1.94×10-4, OR 1.19; rs4958881 pMH=3.26×10-5, OR 1.19; rs3792783 pMH=2.16×10-4, 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 anticentromere- 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.
AB - 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 pMH=1.94×10-4, OR 1.19; rs4958881 pMH=3.26×10-5, OR 1.19; rs3792783 pMH=2.16×10-4, 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 anticentromere- 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.
U2 - 10.1136/annrheumdis-2012-201888
DO - 10.1136/annrheumdis-2012-201888
M3 - Article
C2 - 22896740
SN - 0003-4967
VL - 72
SP - 602
EP - 607
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 4
ER -