Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Functional Variants in the Pre-B Cell Colony Enhancing Factor Gene Are Associated with Systemic Sclerosis Susceptibility and the Clinical Hallmark Pulmonary Arterial Hypertension.

Broen9,  Jasper, Gourh7,  Pravitt, Vonk9,  Madelon, Beretta10,  Lorenzo, Rueda8,  Blanca, Geurts-van Bon9,  Lenny, Brouwer9,  Christel

Centre for Rheumatology, Royal Free and University College Medical School, London, United Kingdom
Referral Center for Systemic Autoimmune Diseases, University of Milan, Italy
Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation Trust, UK
Servicio de Medicina Interna, Hospital Clinico Universitario, Granada, Spain.
Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Oviedo, Spain.
Servicio de Medinina Interna, Hospital Valle de Hebron, Barcelona, Spain
Servizio di Reumatologia ed Immunologia Clinica, Spedali Civili, Brescia, Italia.
University Hospital Zurich Div. of Rheumatology Zurich, Switzerland.
Department of Dermatology, University of Cologne, Germany
Department of Human Genetics, Radboud University Nijmegen Medical Center, The Netherlands
Department of Internal Medicine, Division of Rheumatology, University of Vienna, Austria
Department of Rheumatology, Lund University Hospital, S-221 85 Lund, Sweden
Dept of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, a Leibniz Institute
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHSC-H), Houston, TX
Instituto de Parasitología y Biomedicina, CSIC, Granada, Spain
Radboud University Medical Center, Department of Rheumatology, Nijmegen, The Netherlands

Systemic sclerosis (SSc) is a rare autoimmune disorder, characterized by severe vasculopathy and fibrosis of the skin and internal organs. The most severe complication is pulmonary artery hypertension (PAH). Several variants in immune regulatory genes have already been implicated in SSc. The PBEF gene plays an important role in immune modulation, and two polymorphisms in the promoterregion, namely PBEF -1001T>G (rs9770242) and PBEF -1543C>T influence the predisposition to pulmonary disease. For this reason we investigated the role of these two polymorphisms in the genetic predisposition to systemic sclerosis (SSc) and clinical phenotype susceptibility in 2737 SSc patients and 1913 healthy controls. In two separate populations and in a meta-analysis, the combined PBEF -1543CC -1001TT genotype, was found associated with SSc susceptibility (P=0.009 OR 1.20 (95%CI: 1.05–1.37). In addition, these subjects showed an increased decline in forced vital capacity (FVC) over 15 years (P=0.02) (RR 1.64, 95% CI: 1.02–2.64) and a higher PBEF serum concentration (P<0.01), compared to carriers of the minor alleles. On the other hand, patients with genotype PBEF -1001TT were at lower risk for PAH development compared to the carriers with genotypes PBEF -1001GG and PBEF -1001TG (P<0.001) (RR 3.29, 95% CI: 1.52–7.12). These results reveal an important role for PBEF in the genetic predisposition to SSc and its clinical hallmark PAH.

To cite this abstract, please use the following information:
Broen, Jasper, Gourh, Pravitt, Vonk, Madelon, Beretta, Lorenzo, Rueda, Blanca, Geurts-van Bon, Lenny, et al; Functional Variants in the Pre-B Cell Colony Enhancing Factor Gene Are Associated with Systemic Sclerosis Susceptibility and the Clinical Hallmark Pulmonary Arterial Hypertension. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :829
DOI: 10.1002/art.28597

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