TY - JOUR
TI - TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: Results from a multicentre EUSTAR study of European caucasian patients
AU - Koumakis, E.
AU - Wipff, J.
AU - Dieudé, P.
AU - Ruiz, B.
AU - Bouaziz, M.
AU - Revillod, L.
AU - Guedj, M.
AU - Distler, J.H.W.
AU - Matucci-Cerinic, M.
AU - Humbert, M.
AU - Riemekasten, G.
AU - Airo, P.
AU - Melchers, I.
AU - Hachulla, E.
AU - Cusi, D.
AU - Wichmann, H.-E.
AU - Hunzelmann, N.
AU - Tiev, K.
AU - Caramaschi, P.
AU - Diot, E.
AU - Kowal-Bielecka, O.
AU - Cuomo, G.
AU - Walker, U.
AU - Czirják, L.
AU - Damjanov, N.
AU - Lupoli, S.
AU - Conti, C.
AU - Müller-Nurasyid, M.
AU - Müller-Ladner, U.
AU - Riccieri, V.
AU - Cracowski, J.-L.
AU - Cozzi, F.
AU - Bournia, V.K.
AU - Vlachoyiannopoulos, P.
AU - Chiocchia, G.
AU - Boileau, C.
AU - Allanore, Y.
JO - Annals of the Rheumatic Diseases
PY - 2012
VL - 71
TODO - 11
SP - 1900-1903
PB - 
SN - 0003-4967, 1468-2060
TODO - 10.1136/annrheumdis-2012-201755
TODO - transforming growth factor beta receptor, ALK1 gene;  article;  BMPR2 gene;  clinical article;  codon;  controlled study;  disease association;  eng gene;  ethnic group;  European Caucasian;  exon;  gene;  gene sequence;  genetic association;  genotype;  human;  priority journal;  pulmonary hypertension;  single nucleotide polymorphism;  systemic sclerosis;  TGFR2 gene, DNA Mutational Analysis;  European Continental Ancestry Group;  Female;  Genetic Predisposition to Disease;  Genotype;  Humans;  Hypertension, Pulmonary;  Male;  Polymorphism, Single Nucleotide;  Receptors, Transforming Growth Factor beta;  Scleroderma, Systemic
TODO - 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.
ER -