Work

COL18A1genotypic associations with endostatin levels and clinical features in pulmonary arterial hypertension: a quantitative trait association study

Year: 2022

Type: article

Abstract: Endostatin (ES) is a circulating peptide derived from collagen XVIII alpha 1 (COL18A1) known to inhibit angiogenesis [1, 2]. Decreased angiogenesis is a feature of pulmonary arterial hypertension (PAH) in animal models [3] and human subjects [4]. Our group has reported strong associations between circulating ES levels and haemodynamics and survival in PAH [5–7]. We have also reported that a missense variant in COL18A1 , which encodes ES, confers lower ES and longer survival, suggesting that variation within the gene contributes to circulating levels [5]. In the current study, we assessed COL18A1 variant associations with clinical phenotypes and outcomes, including COL18A1 associations with circulating ES levels, in a large, multicentre PAH cohort in which we previously investigated ES as a prognostic biomarker [6]. Variation around the COL18A1 gene, which encodes the angiostatic peptide endostatin, may influence disease heterogeneity in pulmonary arterial hypertension Exome sequencing and genotyping data were generated by Regeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY, USA.

Source: ERJ Open Research

DOI: 10.1183/23120541.00725-2021