TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: Results from a multicentre EUSTAR study of European caucasian patients

Eugénie Koumakis, Julien Wipff, Philippe Dieudé, Barbara Ruiz, Matthieu Bouaziz, Lucile Revillod, Mickaël Guedj, Jörg H.W. Distler, Marco Matucci-Cerinic, Marc Humbert, Gabriella Riemekasten, Paolo Airo, Inga Melchers, Eric Hachulla, Daniele Cusi, H. Erich Wichmann, Nicolas Hunzelmann, Kiet Tiev, Paola Caramaschi, Elisabeth DiotOtylia Kowal-Bielecka, Giovanna Cuomo, Ulrich Walker, László Czirják, Nemanja Damjanov, Sara Lupoli, Costanza Conti, Martina Müller-Nurasyid, Ulf Müller-Ladner, Valeria Riccieri, Jean Luc Cracowski, Franco Cozzi, Vasiliki Kalliopi Bournia, P. Vlachoyiannopoulos, Gilles Chiocchia, Catherine Boileau, Yannick Allanore

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13 Citations (Scopus)

Abstract

Introduction: Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH. Objective: To explore the genetic bases of SSc-PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. Materials and methods: TGFβ receptor genes, BMPR2, ALK1, TGFR2 and ENG, were sequenced in 10 SSc-PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a fi rst set of 824 French Caucasian SSc patients (including 54 SSc-PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc-PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. Results: No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc-PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc-PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. Conclusions: This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc-PAH using both sequencing and genotyping methods.

Original languageEnglish
Pages (from-to)1900-1903
Number of pages4
JournalAnnals of the rheumatic diseases
Volume71
Issue number11
DOIs
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

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

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    Koumakis, E., Wipff, J., Dieudé, P., Ruiz, B., Bouaziz, M., Revillod, L., Guedj, M., Distler, J. H. W., Matucci-Cerinic, M., Humbert, M., Riemekasten, G., Airo, P., Melchers, I., Hachulla, E., Cusi, D., Wichmann, H. E., Hunzelmann, N., Tiev, K., Caramaschi, P., ... Allanore, Y. (2012). TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: Results from a multicentre EUSTAR study of European caucasian patients. Annals of the rheumatic diseases, 71(11), 1900-1903. https://doi.org/10.1136/annrheumdis-2012-201755