Common variants in OSMR contribute to carotid plaque vulnerability

BackgroundOncostatin 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).nnMethods and resultsWe 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.nnWe 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 ({beta} = 0.118 {+/-} s.e. = 0.040, p = 3.00x2-3, C allele). With respect to different plaque phenotypes, this variant showed strongest associations with intraplaque fat ({beta} = 0.248 {+/-} s.e. = 0.088, p = 4.66x2-3, C allele) and collagen content ({beta} = -0.259 {+/-} s.e. = 0.095, p = 6.22x2-3, C allele). No associations were found for rs10491509 in the LIFR locus.nnConclusionOur study suggests that genetically decreased arterial OSMR expression, possibly resulting in decreased OSM signaling, contributes to increased carotid plaque vulnerability.