Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic parameters in patients with pulmonary arterial hypertension.
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Identificadores
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Fecha de publicación
2014Título de revista
PLoS One
Tipo de contenido
Artigo
DeCS
Receptores de Activinas Tipo II | Receptores de Proteínas Morfogenéticas Óseas de Tipo II | Hipertensión Pulmonar | Canal de Potasio Kv1.5 | MutaciónMeSH
Activin Receptors, Type II | Bone Morphogenetic Protein Receptors, Type II | Hypertension, Pulmonary | Kv1.5 Potassium Channel | MutationResumen
Background: Pulmonary arterial hypertension (PAH) is a rare and progressive vascular disorder characterized by increased pulmonary vascular resistance and right heart failure. The aim of this study was to analyze the Bone Morphogenetic Protein Receptor 2 (BMPR2), Activin A type II receptor like kinase 1 (ALK1/ACVRL1) and potassium voltage-gated channel, shakerrelated subfamily, member 5 (KCNA5) genes in patients with idiopathic and associated PAH. Correlation among pathogenic mutations and clinical and functional parameters was further analyzed.
Methods and results: Forty one patients and fifty controls were included in this study. Analysis of BMPR2, ACVRL1 and KCNA5 genes was performed by polymerase chain reaction (PCR) and direct sequencing. Fifty one nucleotide changes were detected in these genes in 40 of the 41 patients; only 22 of these changes, which were classified as pathogenic, have been detected in 21 patients (51.2%). Ten patients (62.5%) with idiopathic PAH and 10 (40%) with associated PAH showed pathogenic mutations in some of the three genes. Several clinical and hemodynamics parameters showed significant differences between carriers and non-carriers of mutations, being more severe in carriers: mean pulmonary artery pressure (p = 0.043), pulmonary vascular resistence (p = 0.043), cardiac index (p = 0.04) and 6 minute walking test (p = 0.02). This differences remained unchanged after adjusting for PAH type (idiopathic vs non idiopathic).
Conclusions: Pathogenic mutations in BMPR2 gene are frequent in patients with idiopathic and associated PAH group I. Mutations in ACVRL1 and KCNA5 are less frequent. The presence of these mutations seems to increase the severity of the disease.
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