@article{3002923,
    title = "TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: Results from a multicentre EUSTAR study of European caucasian patients",
    author = "Koumakis, E. and Wipff, J. and Dieudé, P. and Ruiz, B. and Bouaziz, M. and Revillod, L. and Guedj, M. and Distler, J.H.W. and Matucci-Cerinic, M. and Humbert, M. and Riemekasten, G. and Airo, P. and Melchers, I. and Hachulla, E. and Cusi, D. and Wichmann, H.-E. and Hunzelmann, N. and Tiev, K. and Caramaschi, P. and Diot, E. and Kowal-Bielecka, O. and Cuomo, G. and Walker, U. and Czirják, L. and Damjanov, N. and Lupoli, S. and Conti, C. and Müller-Nurasyid, M. and Müller-Ladner, U. and Riccieri, V. and Cracowski, J.-L. and Cozzi, F. and Bournia, V.K. and Vlachoyiannopoulos, P. and Chiocchia, G. and Boileau, C. and Allanore, Y.",
    journal = "Annals of the Rheumatic Diseases",
    year = "2012",
    volume = "71",
    number = "11",
    pages = "1900-1903",
    issn = "0003-4967, 1468-2060",
    doi = "10.1136/annrheumdis-2012-201755",
    keywords = "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",
    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."
}