title: Analysis of endothelin-1 and endothelin-1 receptor A gene polymorphisms in patients with pulmonary arterial hypertension.
abstract: 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 ± 0.6 vs. 2.3 ± 0.6; p = 0.05) and a higher indexed pulmonary vascular resistance (18.8 ± 9.6 vs. 14.2 ± 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.
authors.affiliation: Division of Cardiology, Monaldi Hospital, Second University of Naples, Via L. Bianchi, 80131, Naples, Italy. paolo.calabro@unina2.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabrò
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Limongelli
authors.forename: Valeria
authors.initials: V
authors.lastname: Maddaloni
authors.forename: Carmine Dario
authors.initials: CD
authors.lastname: Vizza
authors.forename: Michele
authors.initials: M
authors.lastname: D'Alto
authors.forename: Raffaella
authors.initials: R
authors.lastname: D'Alessandro
authors.forename: Roberto
authors.initials: R
authors.lastname: Poscia
authors.forename: Paola
authors.initials: P
authors.lastname: Argiento
authors.forename: Brunella
authors.initials: B
authors.lastname: Ziello
authors.forename: Roberto
authors.initials: R
authors.lastname: Badagliacca
authors.forename: Emanuele
authors.initials: E
authors.lastname: Romeo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pacileo
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Russo
authors.forename: Francesco
authors.initials: F
authors.lastname: Fedele
authors.forename: Raffaele
authors.initials: R
authors.lastname: Calabrò
mesh_terms: D000328:Adult; D000368:Aged; D019332:Endothelin-1 / Q000235:genetics*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D044022:Receptor, Endothelin A / Q000235:genetics*
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A