RT Journal Article SR Electronic T1 Common variants in OSMR contribute to carotid plaque vulnerability JF bioRxiv FD Cold Spring Harbor Laboratory SP 576793 DO 10.1101/576793 A1 D. van Keulen A1 I. D. van Koeverden A1 A. Boltjes A1 H. M. G. Princen A1 A. J. van Gool A1 G.J. de Borst A1 F.W. Asselbergs A1 D. Tempel A1 G. Pasterkamp A1 S.W. van der Laan YR 2019 UL http://biorxiv.org/content/early/2019/03/14/576793.abstract AB Background Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in OSM and its receptors, OSMR and LIFR, on overall plaque vulnerability (based on macrophage, collagen, smooth muscle cell and fat content) and on seven individual atherosclerotic plaque phenotypes (calcification, collagen, atheroma size, macrophages, smooth muscle cells, vessel density and intraplaque hemorrhage).Methods and results We queried Genotype-Tissue Expression (GTEx) data and selected one variant, rs13168867 (C allele), that associated with decreased OSMR expression and one variant, rs10491509 (A allele), that associated with increased LIFR expression in arterial tissue. No variant was associated to significantly altered OSM expression.We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. The rs13168867 variant in OSMR was significantly associated with an increased overall plaque vulnerability (β = 0.118 ± s.e. = 0.040, p = 3.00×2−3, C allele). With respect to different plaque phenotypes, this variant showed strongest associations with intraplaque fat (β = 0.248 ± s.e. = 0.088, p = 4.66×2−3, C allele) and collagen content (β = −0.259 ± s.e. = 0.095, p = 6.22×2−3, C allele). No associations were found for rs10491509 in the LIFR locus.Conclusion Our study suggests that genetically decreased arterial OSMR expression, possibly resulting in decreased OSM signaling, contributes to increased carotid plaque vulnerability.