Analysis of endothelin-1 and endothelin-1 receptor A gene polymorphisms in patients with pulmonary arterial hypertension

作者：Calabro Paolo^*; Limongelli Giuseppe; Maddaloni Valeria; Vizza Carmine Dario; D' Alto Michele; D' Alessandro Raffaella; Poscia Roberto; Argiento Paola; Ziello Brunella; Badagliacca Roberto; Romeo Emanuele; Pacileo Giuseppe; Russo Maria Giovanna; Fedele Francesco; Calabro Raffaele

来源：Internal and Emergency Medicine, 2012, 7(5): 425-430.

DOI：10.1007/s11739-011-0643-2

• Polymorphism
• Endothelin 1
• Endothelin receptors
• Pulmonary artery hypertension

This study analyses the frequency and the potential role of two polymorphisms, the +134del/insA, located in the gene encoding for Endothelin-1 (EDN1), and the His323His in the gene encoding for Endothelin receptor type A (EDNRA) in a cohort of 98 consecutive patients with pulmonary arterial hypertension from two different Cardiology Units (Mid-South of Italy), and in 100 healthy Caucasian subjects randomly recruited from the same area. Cardiac anatomy and function were analysed by non invasive diagnostic imaging techniques (Echocardiography standard m-mode, 2D, colour-Doppler) and by invasive studies (cardiac catheterization). Molecular screening of the region of interest was performed by automated sequencing. At univariate analysis, patients with the His323His TT genotype show a lower cardiac index (2 +/- A 0.6 vs. 2.3 +/- A 0.6; p = 0.05) and a higher indexed pulmonary vascular resistance (18.8 +/- A 9.6 vs. 14.2 +/- A 6.9; p = 0.01) at cardiac catheterization. A logistic multivariate model shows idiopathic disease (p = 0.01; OR = 3.8; CI = 1.3-11) and indexed pulmonary vascular resistances (p = 0.01; OR = 1.1; CI = 1-1.2) as independent predictors of TT genotype. Our findings may suggest a potential link between specific genotypes in the EDNRA gene and susceptibility for PAH.

• 出版日期2012-10