Περίληψη:
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.
Συγγραφείς:
Koumakis, E.
Wipff, J.
Dieudé, P.
Ruiz, B.
Bouaziz, M.
Revillod, L.
Guedj, M.
Distler, J.H.W.
Matucci-Cerinic, M.
Humbert, M.
Riemekasten, G.
Airo, P.
Melchers, I.
Hachulla, E.
Cusi, D.
Wichmann, H.-E.
Hunzelmann, N.
Tiev, K.
Caramaschi, P.
Diot, E.
Kowal-Bielecka, O.
Cuomo, G.
Walker, U.
Czirják, L.
Damjanov, N.
Lupoli, S.
Conti, C.
Müller-Nurasyid, M.
Müller-Ladner, U.
Riccieri, V.
Cracowski, J.-L.
Cozzi, F.
Bournia, V.K.
Vlachoyiannopoulos, P.
Chiocchia, G.
Boileau, C.
Allanore, Y.
Λέξεις-κλειδιά:
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
