Durst Ronen, Neumark Yehuda, Meiner Vardiella, Friedlander Yechiel, Sharon Nir, Polak Arthur, Beeri Ronen, Danenberg Haim, Erez Gilli, Spitzen Shoshi, Ben-Avi Liat, Leitersdorf Eran, Lotan Chaim
Department of Cardiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Genet Test Mol Biomarkers. 2009 Oct;13(5):583-7. doi: 10.1089/gtmb.2009.0048.
Macrophage scavenger receptor 1 (MSR1) mediates the uptake of modified low density lipoprotein (LDL)-cholesterol. The significance of MSR1 in atherosclerosis development in animal models is uncertain. In this study we sought to determine the significance of MSR1 polymorphisms in its encoding gene in susceptibility to atherosclerosis.
We genotyped three polymorphic sites in the MSR1 gene including a 3-bp "TTA" insertion-deletion in intron 7 (rs3036811, Indel 7), an intron 5 SNP (rs33959637, IVS5-59), and a missense coding single nucleotide polymorphism (SNP) in exon 6 (rs3747531, P275A) in 136 nondiabetic Ashkenazi men under age 55 years (mean = 47.3 +/- 4.8 years) undergoing coronary angiography. Assessment of coronary disease was done by the number of segments with stenosis greater than 20% (coronary artery narrowing greater than 20% [CAGE > 20%]), greater than 50% (CAGE > 50%), and total number of diseased vessels. Linear regression modeling was used to define associations between atherosclerotic burden and MSR1 SNPs and haplotypes.
Significant associations were noted between IVS5-59 and number of diseased vessels (p = 0.009) and CAGE > 20% (p = 0.017), which remained significant upon controlling for age, cholesterol level, hypertension, and smoking.
This study demonstrates an association between MSR1 polymorphisms and atherosclerosis, suggesting that atherosclerotic risk associated with classic risk factors may be modified by MSR1 polymorphisms. These findings point to a significant role of MSR1 in atherosclerosis.
巨噬细胞清道夫受体1（MSR1）介导修饰的低密度脂蛋白（LDL）胆固醇的摄取。MSR1在动物模型动脉粥样硬化发展中的意义尚不确定。在本研究中，我们试图确定MSR1编码基因中的多态性在动脉粥样硬化易感性中的意义。
我们对136名年龄在55岁以下（平均 = 47.3 +/- 4.8岁）接受冠状动脉造影的非糖尿病阿什肯纳兹男性的MSR1基因中的三个多态性位点进行基因分型，包括内含子7中的一个3碱基“TTA”插入缺失（rs3036811，Indel 7）、内含子5单核苷酸多态性（SNP）（rs33959637，IVS5 - 59）和外显子6中的一个错义编码单核苷酸多态性（SNP）（rs3747531，P275A）。通过狭窄大于20%的节段数（冠状动脉狭窄大于20% [CAGE > 20%]）、大于50%的节段数（CAGE > 50%）以及病变血管总数来评估冠状动脉疾病。使用线性回归模型来确定动脉粥样硬化负担与MSR1 SNPs及单倍型之间的关联。
IVS5 - 59与病变血管数（p = 0.009）和CAGE > 20%（p = 0.017）之间存在显著关联，在控制年龄、胆固醇水平、高血压和吸烟因素后，这些关联仍然显著。
本研究证明了MSR1多态性与动脉粥样硬化之间的关联，表明与经典危险因素相关的动脉粥样硬化风险可能会因MSR1多态性而改变。这些发现表明MSR1在动脉粥样硬化中起重要作用。
