4.6 Article

Association between OLR1 K167N SNP and Intima Media Thickness of the Common Carotid Artery in the General Population

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PLOS ONE
卷 7, 期 2, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0031086

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资金

  1. Research for Drug Development
  2. Fondazione G. B. Bietti (ONLUS)
  3. Fondazione Umberto Veronesi per il progresso delle Scienze and Societa Italiana Studio Aterosclerosi Lombardia Chapter
  4. Istituto Nazionale Ricerca Cardiovascolari
  5. ASPREMARE
  6. Istituto di Ricovero e Cura a Carattere Scientifico Multimedica
  7. National Institutes of Health [2T32HL007751-16A2]

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Background and Purpose: The 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). Results: Significantly 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. Conclusions: These 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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