ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2303

Confirmation of TNIP1 As a Susceptibility Locus for Systemic Sclerosis in a Large Multicentre Study

Lara Bossini-Castillo1, Jose Ezequiel Martin2, Carmen Pilar Simeon3, Lorenzo Beretta4, Olga Y. Gorlova5, Madelon C. Vonk6, Patricia Carreira7, the Spanish Scleroderma Group8, Annemie Schuerwegh9, Alexandre Voskuyl10, Anna-Maria Hoffmann-Vold11, Roger Hesselstrand12, Annika Nordin13, Claudio Lunardi14, Jaap Van Laar15, Paul Shiels16, Ariane Herrick17, Jane Worthington18, Carmen Fonseca19, Christopher P. Denton19, Shervin Assassi20, Bobby P.C. Koeleman21, Maureen D. Mayes22, T.R.D.J. Radstake23 and Javier Martin1, 1Immunology, Instituto de Parasitologia y Biomedicina Lopez-Neyra (IPBLN-CSIC), Granada, Spain, 2Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla (Granada), Spain, 3Servicio de Medicina Interna, Hospital Valle de Hebron, Barcelona, Spain, 4Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy, 5Department of Epidemiology, UT M. D. Anderson Cancer Center, Houston, TX, 6Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 7Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain, 8Granada, Spain, 9Leids Univ Medisch Centrum, Leiden, Netherlands, 10Department of Rheumatology, VU University Medical Center, Amsterdam, Netherlands, 11Rheumatology, Oslo University Hospital, Oslo, Norway, 12Rheumatology, Lund University, Lund, Sweden, 13Department of Rheumatology, Karolinska Institute, Stockholm, Sweden, 14Department of Medicine, Università degli Studi di Verona, Verona, Italy, 15Rheumatology, Leiden University Hospital, Leiden, Netherlands, 16University of Glasgow, Glasgow, United Kingdom, 17Musculoskeletal Research Group, University of Manchester, Salford, United Kingdom, 18Arthritis Research UK Epidemiology Unit, Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom, 19Centre for Rheumatology, Royal Free and University College Medical School, London, United Kingdom, 20Internal Medicine/Rheumatology, University of Texas Health Science Center at Houston, Houston, TX, 21Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands, 22Rheumatology, University of Texas Health Science Center at Houston, Houston, TX, 23Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s – Pathogenesis, Animal Models and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose: Systemic sclerosis or scleroderma (SSc) is a complex autoimmune disorder that affects the connective tissue causing fibrosis in the skin and different internal organs. A recent genome-wide association study (GWAS) in European SSc patients identified three loci as novel genetic risk factors for the disease (RHOB, PSORS1C1 and TNIP1). The latter two have a well-known role in autoimmune disease genetic susceptibility. PSORS1C1 (Psoriasis susceptibility 1 candidate 1) is located in the vicinity of HLA class I region and has been identified as a psoriasis genetic risk factor. Polymorphisms in TNIP1 (TNFAIP3 interacting protein 1) have been related to a number of autoimmune disorders and the protein encoded by this gene is involved in the NF-κβ signaling pathway. The aim of our study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry.

Methods: 4,389 SSc patients and 7,611 healthy controls from different European countries and the US were included in this study. Six single nucleotide polymorphisms (SNPs): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analyzed. Plink was used for the statistical analyses. Overall significance was calculated by pooled-analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to further explore the genetic structure of the tested loci.

Results: Pooled-analyses of all the analyzed 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 considered subgroups. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the ACA+ 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.

Conclusion: Our data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor.

Disclosure:

L. Bossini-Castillo,
None;

J. E. Martin,
None;

C. P. Simeon,
None;

L. Beretta,
None;

O. Y. Gorlova,
None;

M. C. Vonk,
None;

P. Carreira,
None;

A. Schuerwegh,
None;

A. Voskuyl,
None;

A. M. Hoffmann-Vold,
None;

R. Hesselstrand,
None;

A. Nordin,
None;

C. Lunardi,
None;

J. Van Laar,
None;

P. Shiels,
None;

A. Herrick,
None;

J. Worthington,
None;

C. Fonseca,
None;

C. P. Denton,
None;

S. Assassi,
None;

B. P. C. Koeleman,
None;

M. D. Mayes,
None;

T. R. D. J. Radstake,
None;

J. Martin,
None.

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