AUTHOR=Liang Kae-Woei , Chang Sheng-Kai , Chen Yu-Wei , Lin Wei-Wen , Tsai Wan-Jane , Wang Kuo-Yang 

TITLE=Whole Exome Sequencing of Patients With Heritable and Idiopathic Pulmonary Arterial Hypertension in Central Taiwan

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.911649

DOI=10.3389/fcvm.2022.911649

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Genetic variants could be identified in subjects with idiopathic and heritable pulmonary arterial hypertension (PAH). The 6th World Symposium on Pulmonary Hypertension (WSPH) provided a list of genes with evidence of association with PAH. However, reports using whole exome sequencing (WES) from southeastern Asian PAH cohorts were scarce.</p></sec><sec><title>Methods</title><p>Subjects with idiopathic and heritable PAH (<italic>N</italic> = 45) from two medical centers in central Taiwan were screened for PAH related gene variants. The genomic DNA was prepared from peripheral blood lymphocytes. We performed WES for all patients enrolled in this study. All identified gene variants were validated by polymerase-chain reaction and Sanger sequencing. The clinical and hemodynamic data were compared between bone morphogenetic protein receptor type-2 (<italic>BMPR2</italic>) gene variants carriers vs. non-carriers.</p></sec><sec><title>Results</title><p>Eight patients (8/45 = 17.8%) was identified carrying <italic>BMPR2</italic> gene variants and 8 patients (8/45 = 17.8%) had other WSPH-listed PAH-related gene variants (1 with <italic>ACVRL1</italic>, 1 with <italic>ENG</italic>, 1 with <italic>SMAD9</italic>, 1 with <italic>SMAD1</italic>, 1 with <italic>ATP13A3</italic> and 3 with <italic>AQP1</italic>). In addition, a total of 14 non-WSPH-listed PAH-related genetic variant sites (<italic>ABCC8, NOTCH1, NOTCH2, NOTCH3, JAG1, BMP10, GGCX, FBLN2, ABCA3</italic> and <italic>PTGIS</italic>) were found in this PAH cohort. Subjects carrying <italic>BMPR2</italic> gene variant (<italic>N</italic> = 8) were younger at diagnosis of PAH (30 ± 11 vs 49 ± 13 years, <italic>p</italic> = 0.001) than the non-carrier group (<italic>N</italic> = 37). <italic>BMPR2</italic> variant carriers had a trend toward having higher mean pulmonary arterial pressure (PAP) (61 ± 19 vs. 51 ± 13 mmHg, <italic>p</italic> = 0.076) than the non-carriers upon initial diagnosis. Pulmonary vascular resistance, right atrial pressure, cardiac output, as well as functional class were similar between <italic>BMPR2</italic> variant carriers and non-carriers at initial diagnosis.</p></sec><sec><title>Conclusions</title><p>We identified 17.8% of patients with <italic>BMPR2</italic> gene variants and 17.8% subjects with other 6th WSPH-listed PAH-related gene variants in a Taiwanese idiopathic and heritable PAH cohort. PAH patients carrying <italic>BMPR2</italic> variants presented at a younger age with a trend toward having higher mean PAP at initial diagnosis.</p></sec>