PT  - JOURNAL ARTICLE
AU  - D. van Keulen
AU  - I. D. van Koeverden
AU  - A. Boltjes
AU  - H. M. G. Princen
AU  - A. J. van Gool
AU  - G.J. de Borst
AU  - F.W. Asselbergs
AU  - D. Tempel
AU  - G. Pasterkamp
AU  - S.W. van der Laan
TI  - Common variants in <em>OSMR</em> contribute to carotid plaque vulnerability
AID  - 10.1101/576793
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 576793
4099  - http://biorxiv.org/content/early/2019/03/14/576793.short
4100  - http://biorxiv.org/content/early/2019/03/14/576793.full
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.