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.

Association between OLR1 K167N SNP and Intima Media Thickness of the Common Carotid Artery in the General Population / I.M. Predazzi, G.D. Norata, L. Vecchione, K. Garlaschelli, F. Amati, L. Grigore, L. Cutuli, A. Pirillo, S. Tramontana, F. Romeo, G. Novelli, A.L. Catapano. - In: PLOS ONE. - ISSN 1932-6203. - 7:2(2012 Feb), pp. e31086.e31086.1-e31086.e31086.6.

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

G.D. Norata;K. Garlaschelli;A. Pirillo;A.L. Catapano
2012-02

Abstract

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.
Settore BIO/14 - Farmacologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
PLoS One 2012_7_e31086.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 198.54 kB
Formato Adobe PDF
198.54 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/171297
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 17
social impact