Pousada Guillermo, Baloira Adolfo, Vilariño Carlos, Cifrian Jose Manuel, Valverde Diana
Department of Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, Instituto de Investigación Biomédica de Vigo (IBIV), Vigo, Spain.
Respiratory Division, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain.
PLoS One. 2014 Jun 17;9(6):e100261. doi: 10.1371/journal.pone.0100261. eCollection 2014.
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.
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).
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.
肺动脉高压（PAH）是一种罕见的进行性血管疾病，其特征为肺血管阻力增加和右心衰竭。本研究旨在分析特发性和相关性PAH患者的骨形态发生蛋白受体2（BMPR2）、激活素A II型受体样激酶1（ALK1/ACVRL1）和钾电压门控通道、震颤相关亚家族成员5（KCNA5）基因。进一步分析致病突变与临床和功能参数之间的相关性。
本研究纳入41例患者和50例对照。通过聚合酶链反应（PCR）和直接测序对BMPR2、ACVRL1和KCNA5基因进行分析。在41例患者中的40例中检测到这些基因的51个核苷酸变化；其中只有22个变化被分类为致病性变化，在21例患者（51.2%）中检测到。10例（62.5%）特发性PAH患者和10例（40%）相关性PAH患者在这三个基因中的一些基因中显示出致病突变。几个临床和血流动力学参数在突变携带者和非携带者之间显示出显著差异，携带者更为严重：平均肺动脉压（p = 0.043）、肺血管阻力（p = 0.043）、心脏指数（p = 0.04）和6分钟步行试验（p = 0.02）。在调整PAH类型（特发性与非特发性）后，这些差异保持不变。
BMPR2基因的致病突变在特发性和相关性PAH I组患者中很常见。ACVRL1和KCNA5中的突变较少见。这些突变的存在似乎增加了疾病的严重程度。
