Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Jaap Van Laar


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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 x 10(-4), OR 1.19; rs4958881 p(MH) = 3.26 x 10(-5), OR 1.19; rs3792783 p(MH) = 2.16 x 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.

Publication metadata

Author(s): Bossini-Castillo L, Martin JE, Broen J, Simeon CP, Beretta L, Gorlova OY, Vonk MC, Ortego-Centeno N, Espinosa G, Carreira P, de la Pena PG, Oreiro N, Roman-Ivorra JA, Castillo MJ, Gonzalez-Gay MA, Saez-Comet L, Castellvi I, Schuerwegh AJ, Voskuyl AE, Hoffmann-Vold AM, Hesselstrand R, Nordin A, Lunardi C, Scorza R, van Laar JM, Shiels PG, Herrick A, Worthington J, Fonseca C, Denton C, Tan FK, Arnett FC, Assassi S, Koeleman BP, Mayes MD, Radstake TRDJ, Martin J, Spanish Scleroderma Grp

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2013

Volume: 72

Issue: 4

Pages: 602-607

Print publication date: 01/04/2013

ISSN (print): 0003-4967

ISSN (electronic):

Publisher: BMJ Group


DOI: 10.1136/annrheumdis-2012-201888


Altmetrics provided by Altmetric


Funder referenceFunder name
Dutch Arthritis Foundation (National Reumafonds)
Orphan Disease Programme grant from the European League Against Rheumatism (EULAR)
Fondo Europeo de Desarrollo Regional (FEDER)
GEN-FER from the Spanish Society of Rheumatology
NIH/NIAMS Scleroderma Registry
VIDI laureate from the Dutch Association of Research (NWO)
1P50AR054144NIH/NIAMS Center of Research Translation in Scleroderma
2008.40.001Dutch Diabetes Research Foundation
1031/6.1DFG WI
CTS-4977Junta de Andalucia, Spain, in part by Redes Tematicas de Investigacion Cooperativa Sanitaria Programme
N01-AR-0-2251DNA Repository
PI-0590-2010Consejeria de Salud, Junta de Andalucia, Spain
NR 09-1-408Dutch Arthritis Foundation (Reumafonds)
W81XWH-07-01-0111Department of Defense Congressionally Directed Medical Research Programmes
RD08/0075 (RIER)Instituto de Salud Carlos III (ISCIII), Spain
SAF2009-11110Spanish Ministry of Science