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  • Poster presentation
  • Open Access

Variants of PBEF predispose to systemic sclerosis and pulmonary arterial hypertension development

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Contributed equally
Journal of Translational Medicine20108 (Suppl 1) :P46

  • Published:


  • Pulmonary Arterial Hypertension
  • Minor Allele
  • Forced Vital Capacity
  • Systemic Sclerosis
  • Functional Polymorphism


Pre B-cell colony-enhancing factor (PBEF) is intricately involved in inflammation and fibrosis, functional polymorphisms of PBEF have been previously shown to influence PBEF expression and pulmonary damage. Systemic sclerosis (SSc) is a disease in which inflammation, fibrosis and pulmonary deterioration are prominent hallmarks. Therefore we here investigate the role of the PBEF -1001T>G and PBEF -1543C>T polymorphisms in the genetic predisposition to systemic sclerosis (SSc) susceptibility and pulmonary involvement.

Patients and methods

We genotyped DNA from 2737 SSc patients and 1913 matched healthy controls, both from 8 different ethnic populations. Genotyping was performed using custom Taqman 5´allelic discrimination assays. In addition, PBEF serum expression levels were measured by ELISA and correlated with genotypes.


In two separate populations and in a meta-analysis, the combined PBEF -1543CC -1001TT genotype, hence carrying no minor alleles, 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 follow-up (P=0.02) (HR 1.64, 95%CI: 1.02-2.64) and a higher PBEF serum concentration (P<0.01), compared to carriers of minor alleles. On the other hand, patients with genotype PBEF -1001TT were at lower risk for PAH development within 15 years of disease onset compared to the carriers with genotypes PBEF-1001GG and PBEF-1001TG (P<0.001) (HR 3.29, 95%CI: 1.52-7.12).


Our data identify PBEF as a novel candidate gene that influences SSc susceptibility, pulmonary function and the development of PAH.


Authors’ Affiliations

Dept. of Rheumatology, Radboud University Nijmegen Medical Center, The Netherlands
Division of Rheumatology and Clinical Immunogenetics, Dept. of Internal Medicine, University of Texas Health Science Center at Houston (UTHSC-H), Houston, TX, USA
Referral Center for Systemic Autoimmune Diseases, University of Milan, Italy
University Hospital Zurich Div. of Rheumatology Zurich, Switzerland
Instituto de Parasitología y Biomedicina, CSIC, Granada, Spain
Dept. of Rheumatology, Lund University Hospital, Lund, Sweden
Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation Trust, UK
Dept. of Dermatology, University of Cologne, Germany
Centre for Rheumatology, Royal Free and University College Medical School, London, UK
Dept.of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, a Leibniz institute, Germany
Dept. of Internal Medicine, division of Rheumatology, University of Vienna, Austria
Servicio de Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain
Servicio de Reumatologia, Hospital 12 de Octubre, Madrid, Spain
Servicio de Medicina Interna, Hospital Clinico Universitario, Granada, Spain
Servicio de Reumatologia, Hospital Marques de Valdecillas, Santander, Spain
Servizio di Reumatologia ed Immunologia Clinica, Spedali Civili, Brescia, Italy
Dept. of Human Genetics, Radboud University Nijmegen Medical Center, The Netherlands


© Broen et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.