@misc{10481/88509,
year = {2013},
url = {https://hdl.handle.net/10481/88509},
abstract = {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)=1.94×10(-4), OR 1.19; rs4958881 p(MH)=3.26×10(-5), OR 1.19; rs3792783 p(MH)=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 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.},
organization = {This work was supported by the following grants: JM was funded by GEN-FER from the Spanish Society
of Rheumatology, SAF2009–11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía,
Spain, in part by Redes Temáticas de Investigación Cooperativa Sanitaria Programme, RD08/0075 (RIER) from
Instituto de Salud Carlos III (ISCIII), Spain and by Fondo Europeo de Desarrollo Regional (FEDER). TRDJR was
funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation
(National Reumafonds). JM and TRDJR were sponsored by the Orphan Disease Programme grant from the
European League Against Rheumatism (EULAR). BPCK is supported by the Dutch Diabetes Research Foundation
(grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). TW was granted by
DFG WI 1031/6.1. This study was also funded by PI-0590-2010, Consejería de Salud, Junta de Andalucía, Spain.
The USA studies were supported by NIH/NIAMS Scleroderma Registry and DNA Repository (N01-AR-0-2251),
NIH/NIAMS-RO1-AR055258 and NIH/NIAMS Center of Research Translation in Scleroderma (1P50AR054144),
and the Department of Defense Congressionally Directed Medical Research Programmes (W81XWH-07-01-0111).},
title = {Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study},
doi = {10.1136/annrheumdis-2013-204591},
author = {Bossini Castillo, Lara and Martín, José-Ezequiel and Ortego Centeno, Norberto and Martín Ibáñez, Javier and Spanish Scleroderma Group},
}