Authors
François Potus, Michael W Pauciulo, Elina K Cook, Na Zhu, Alexander Hsieh, Carrie L Welch, Yufeng Shen, Lian Tian, Patricia Lima, Jeffrey Mewburn, Christine L D’Arsigny, Katie A Lutz, Anna W Coleman, Rachel Damico, Brooke Snetsinger, Ashley Y Martin, Paul M Hassoun, William C Nichols, Wendy K Chung, Michael J Rauh, Stephen L Archer
Publication date
2020/6/16
Journal
Circulation
Volume
141
Issue
24
Pages
1986-2000
Publisher
Lippincott Williams & Wilkins
Description
Background
Pulmonary arterial hypertension (PAH) is a lethal vasculopathy. Hereditary cases are associated with germline mutations in BMPR2 and 16 other genes; however, these mutations occur in <25% of patients with idiopathic PAH and are rare in PAH associated with connective tissue diseases. Preclinical studies suggest epigenetic dysregulation, including altered DNA methylation, promotes PAH. Somatic mutations of Tet-methylcytosine-dioxygenase-2 (TET2), a key enzyme in DNA demethylation, occur in cardiovascular disease and are associated with clonal hematopoiesis, inflammation, and adverse vascular remodeling. The role of TET2 in PAH is unknown.
Methods
To test for a role of TET2, we used a cohort of 2572 cases from the PAH Biobank. Within this cohort, gene-specific rare variant association tests were performed using 1832 unrelated European patients with PAH and 7509 non-Finnish …
Scholar articles
F Potus, MW Pauciulo, EK Cook, N Zhu, A Hsieh… - Circulation, 2020