Koumakis, Eugénie (34971474300)Eugénie (34971474300)KoumakisWipff, Julien (23029201600)Julien (23029201600)WipffDieudé, Philippe (56206750400)Philippe (56206750400)DieudéRuiz, Barbara (25641775300)Barbara (25641775300)RuizBouaziz, Matthieu (50561104500)Matthieu (50561104500)BouazizRevillod, Lucile (57194549913)Lucile (57194549913)RevillodGuedj, Mickaël (16241329100)Mickaël (16241329100)GuedjDistler, Jörg H. W. (7005411651)Jörg H. W. (7005411651)DistlerMatucci-Cerinic, Marco (7005642558)Marco (7005642558)Matucci-CerinicHumbert, Marc (55382766900)Marc (55382766900)HumbertRiemekasten, Gabriella (57203073213)Gabriella (57203073213)RiemekastenAiro, Paolo (7003811242)Paolo (7003811242)AiroMelchers, Inga (57202772011)Inga (57202772011)MelchersHachulla, Eric (35377410100)Eric (35377410100)HachullaCusi, Daniele (7004967345)Daniele (7004967345)CusiWichmann, H.-Erich (7102574024)H.-Erich (7102574024)WichmannHunzelmann, Nicolas (24474793400)Nicolas (24474793400)HunzelmannTiev, Kiet (10040839700)Kiet (10040839700)TievCaramaschi, Paola (35375354000)Paola (35375354000)CaramaschiDiot, Elisabeth (7004393217)Elisabeth (7004393217)DiotKowal-Bielecka, Otylia (8538884500)Otylia (8538884500)Kowal-BieleckaCuomo, Giovanna (58021681500)Giovanna (58021681500)CuomoWalker, Ulrich (7003907112)Ulrich (7003907112)WalkerCzirják, László (7004435091)László (7004435091)CzirjákDamjanov, Nemanja (8503557800)Nemanja (8503557800)DamjanovLupoli, Sara (26433631200)Sara (26433631200)LupoliConti, Costanza (35781657400)Costanza (35781657400)ContiMüller-Nurasyid, Martina (57202315232)Martina (57202315232)Müller-NurasyidMüller-Ladner, Ulf (59157641100)Ulf (59157641100)Müller-LadnerRiccieri, Valeria (7003568453)Valeria (7003568453)RiccieriCracowski, Jean-Luc (7005878536)Jean-Luc (7005878536)CracowskiCozzi, Franco (35271801400)Franco (35271801400)CozziBournia, Vasiliki Kalliopi (25935824800)Vasiliki Kalliopi (25935824800)BourniaVlachoyiannopoulos, P. (7003280348)P. (7003280348)VlachoyiannopoulosChiocchia, Gilles (55068614500)Gilles (55068614500)ChiocchiaBoileau, Catherine (57203196621)Catherine (57203196621)BoileauAllanore, Yannick (7003519327)Yannick (7003519327)Allanore2025-07-022025-07-022012https://doi.org/10.1136/annrheumdis-2012-201755https://www.scopus.com/inward/record.uri?eid=2-s2.0-84867404076&doi=10.1136%2fannrheumdis-2012-201755&partnerID=40&md5=05afad2baf035ac4c0b4b5112bd780d9https://remedy.med.bg.ac.rs/handle/123456789/13926Introduction: 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.