TGF{beta} receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients
Annals of Rheumatic Diseases, 08/21/2012
Koumakis E et al. – This study demonstrates the lack of association between these transforming growth factor beta receptor gene polymorphisms and systemic sclerosis–pulmonary arterial hypertension using both sequencing and genotyping methods.
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.
- 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.
