Department of Biopathology and Diagnostic Imaging, Section of Medical Genetics, School of Medicine, Tor Vergata University, Rome, Italy.
PLoS One. 2012;7(2):e31086. doi: 10.1371/journal.pone.0031086. Epub 2012 Feb 9.
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.
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).
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.
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.
凝集素样氧化型 LDL 受体-1（OLR1）基因编码一种参与动脉粥样硬化发病机制的清道夫受体。虽然已经提出了两种变体的功能作用，但 OLR1 的流行病学研究一直存在不一致。
我们在来自颈动脉内膜进展（PLIC）研究（一项前瞻性基于人群的研究）的 2141 个样本中测试了非 synonymous替换 K167N（rs11053646）与颈总动脉内膜中层厚度（CCA-IMT）之间的关联。
与 GC 和 GG（KN 和 KK）基因型相比，男性携带次要 C（N）等位基因的个体 IMT 明显增加。对巨噬细胞的功能分析表明，与 KN 和 KK 携带者相比，NN 携带者与 Ox-LDL 的关联降低，这也与 OLR1 mRNA 表达降低有关。与 KN 和 KK 携带者的细胞相比，NN 携带者的巨噬细胞也表现出特定的炎症基因表达模式。
这些数据表明，LOX-1 受体的 167N 变体通过炎症过程影响颈动脉疾病发生前的动脉粥样硬化过程。
