18 research outputs found
The influence of anti-cyclic citrullinated peptide on anticentromere antibody-positive rheumatoid arthritis patients: authors' response
Emerging drugs for the treatment of scleroderma: a review of recent phase 2 and 3 trials
Meta-Analysis of Anti-Muscarinic Receptor Type 3 Antibodies for the Diagnosis of Sjögren Syndrome
Clinical and serological characteristics of seronegative primary Sjögren’s syndrome: a comparative study
TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients.
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 first 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