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 first 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.
TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension : results from a multicentre EUSTAR study of European Caucasian patients / E. Koumakis, J. Wipff, P. Dieudé, B. Ruiz, M. Bouaziz, L. Revillod, M. Guedj, J.H. Distler, M. Matucci-Cerinic, M. Humbert, G. Riemekasten, P. Airo, I. Melchers, E. Hachulla, D. Cusi, H.E. Wichmann, N. Hunzelmann, K. Tiev, P. Caramaschi, E. Diot, O. Kowal-Bielecka, G. Cuomo, U. Walker, L. Czirják, N. Damjanov, S. Lupoli, C. Conti, M. Müller-Nurasyid, U. Müller-Ladner, V. Riccieri, J.L. Cracowski, F. Cozzi, V.K. Bournia, P. Vlachoyiannopoulos, G. Chiocchia, C. Boileau, Y. Allanore. - In: ANNALS OF THE RHEUMATIC DISEASES. - ISSN 0003-4967. - 71:11(2012 Nov), pp. 1900-1903.
|Titolo:||TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension : results from a multicentre EUSTAR study of European Caucasian patients|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||nov-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1136/annrheumdis-2012-201755|
|Appare nelle tipologie:||01 - Articolo su periodico|