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

Lara Bossini-Castillo, Jose Ezequiel Martin, Jasper Broen, Carmen P. Simeon, Lorenzo Beretta, Olga Y. Gorlova, Madelon C. Vonk, Norberto Ortego-Centeno, Gerard Espinosa, Patricia Carreira, Paloma García De La Peña, Natividad Oreiro, José Andrés Román-Ivorra, María Jesús Castillo, Miguel A. González-Gay, Luis Sáez-Comet, Ivan Castellví, Annemie J. Schuerwegh, Alexandre E. Voskuyl, Anna Maria Hoffmann-VoldRoger Hesselstrand, Annika Nordin, Claudio Lunardi, Raffaella Scorza, Jacob M. Van Laar, Paul G. Shiels, Ariane Herrick, Jane Worthington, Carmen Fonseca, Christopher Denton, Filemon K. Tan, Frank C. Arnett, Shervin Assassi, Bobby P. Koeleman, Maureen D. Mayes, Timothy R D J Radstake, Javier Martin

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)602-607
Number of pages6
JournalAnnals of the Rheumatic Diseases
Issue number4
Publication statusPublished - Apr 2013

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy


Dive into the research topics of 'Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study'. Together they form a unique fingerprint.

Cite this