TY - JOUR
T1 - Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population
AU - Predazzi, Irene Marta
AU - Norata, Giuseppe Danilo
AU - Vecchione, Lucia
AU - Garlaschelli, Katia
AU - Amati, Francesca
AU - Grigore, Liliana
AU - Cutuli, Lucia
AU - Pirillo, Angela
AU - Tramontana, Simona
AU - Romeo, Francesco
AU - Novelli, Giuseppe
AU - Catapano, Alberico Luigi
PY - 2012/2/9
Y1 - 2012/2/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84856775548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856775548&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0031086
DO - 10.1371/journal.pone.0031086
M3 - Article
C2 - 22347434
AN - SCOPUS:84856775548
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e31086
ER -