Abstract 213: Human Genetic Variations in Neuroimmune Guidance Cues and their Role in Premature Atherosclerosis

Introduction: Neuroimmune guidance cues (NGCs), a family of proteins originally known for controlling neuronal migration, have been shown to be involved in atherosclerosis in mice models by regulating adhesion of monocytes to the vascular endothelium. The NGC family consists of multiple receptors and ligands enabling an interplay between inflammatory cells and the vasculature endothelium. We set out to investigate the role of NGCs in atherosclerosis in humans. Methods and results: We sequenced a total of 77 NGC genes in a unique cohort of 89 patients with premature atherosclerotic (PAS), in whom no clear CVD risk factor was present. A total of 178 rare variants were identified and we classified the pathogenicity of these rare (MAFu003c0.05) variants by high Combined Annotation Dependent Depletion (CADD) scores. Based on literature and cosegregating pedigrees of the 88 possible deleterious variants we chose two variants in Netrin1 (NTN1) and EphrinB2 (EFNB2) to explore and validate their causality in human ath...