TY - JOUR
T1 - TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: Results from a multicentre EUSTAR study of European caucasian patients
AU - Koumakis, Eugénie
AU - Wipff, Julien
AU - Dieudé, Philippe
AU - Ruiz, Barbara
AU - Bouaziz, Matthieu
AU - Revillod, Lucile
AU - Guedj, Mickaël
AU - Distler, Jörg H.W.
AU - Matucci-Cerinic, Marco
AU - Humbert, Marc
AU - Riemekasten, Gabriella
AU - Airo, Paolo
AU - Melchers, Inga
AU - Hachulla, Eric
AU - Cusi, Daniele
AU - Wichmann, H. Erich
AU - Hunzelmann, Nicolas
AU - Tiev, Kiet
AU - Caramaschi, Paola
AU - Diot, Elisabeth
AU - Kowal-Bielecka, Otylia
AU - Cuomo, Giovanna
AU - Walker, Ulrich
AU - Czirják, László
AU - Damjanov, Nemanja
AU - Lupoli, Sara
AU - Conti, Costanza
AU - Müller-Nurasyid, Martina
AU - Müller-Ladner, Ulf
AU - Riccieri, Valeria
AU - Cracowski, Jean Luc
AU - Cozzi, Franco
AU - Bournia, Vasiliki Kalliopi
AU - Vlachoyiannopoulos, P.
AU - Chiocchia, Gilles
AU - Boileau, Catherine
AU - Allanore, Yannick
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84867404076&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2012-201755
DO - 10.1136/annrheumdis-2012-201755
M3 - Journal articles
C2 - 22896741
AN - SCOPUS:84867404076
VL - 71
SP - 1900
EP - 1903
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 11
ER -