Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population |
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Authors: | Predazzi Irene Marta Norata Giuseppe Danilo Vecchione Lucia Garlaschelli Katia Amati Francesca Grigore Liliana Cutuli Lucia Pirillo Angela Tramontana Simona Romeo Francesco Novelli Giuseppe Catapano Alberico Luigi |
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Affiliation: | Department of Biopathology and Diagnostic Imaging, Section of Medical Genetics, School of Medicine, Tor Vergata University, Rome, Italy. irene.m.predazzi@Vanderbilt.Edu |
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Abstract: | Background and PurposeThe lectin-like oxidised LDL receptor-1 (OLR1) gene encodes a scavenger receptor implicated in the pathogenesis of atherosclerosis. Although functional roles have been suggested for two variants, epidemiological studies on OLR1 have been inconsistent.Methods - We tested the association between the non-synonymous substitution K167N (rs11053646) and intima media thickness of the common carotid artery (CCA-IMT) in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study).ResultsSignificantly increased IMT was observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotype. Functional analysis on macrophages suggested a decreased association to Ox-LDL in NN carriers compared to KN and KK carriers which is also associated with a reduced OLR1 mRNA expression. Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers.ConclusionsThese data suggest that the 167N variant of LOX-1 receptor affects the atherogenic process in the carotid artery prior to evidence of disease through an inflammatory process. |
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