Laboratory for Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinča, University of Belgrade, Belgrade, Serbia.
Mol Biol Rep. 2012 Jun;39(6):6479-85. doi: 10.1007/s11033-012-1475-5. Epub 2012 Feb 4.
Atherosclerosis is known as an inflammatory disease in which a recruitment of leukocytes to the endothelium wall represents a preliminary step of the initiation and the development of disease. The P-selectin glycoprotein ligand (PSGL-1) seems to be the major molecule mediating leukocyte-endothelium interactions and leukocyte rolling on stimulated endothelium. There are limited number of studies reporting on association of Met62Ile SNP in PSGL-1 gene and the risk for atherosclerosis. The aim of this study was to analyze possible association of this polymorphism with an advanced carotid atherosclerosis and biochemical markers of inflammation and haemostasis. The 275 patients consecutively admitted for carotid endarterectomy with stenosis >70% and 256 controls of the same ethnic origin were included in the study. The Met62Ile genotypes were determined by PCR RFLP. The Ile/Ile homozygotes had significantly higher CRP compared to the other genotypes in patients. Female patients had Ile allele dose-dependent association with the carotid plaque presence (Met/Met vs. Met/Ile vs. Ile/Ile; OR 1, OR 2.02, CI 1.0-4.08, OR 4.08, CI 1.0-16.81, respectively, p = 0.04). Our results suggest the impact of PSGL-1 Met62Ile polymorphism on inflammation in advanced atherosclerosis. We observed the sex-differential association of Met62Ile with advanced carotid atherosclerosis. Studies in larger and different populations should validate and further examine the suggested role of genetic variations in PSGL-1 with atherosclerosis and thrombosis.
动脉粥样硬化是一种炎症性疾病,其中白细胞募集到血管内皮壁代表疾病发生和发展的初步步骤。P-选择素糖蛋白配体(PSGL-1)似乎是介导白细胞-内皮细胞相互作用和白细胞在受刺激的内皮上滚动的主要分子。有有限数量的研究报告 PSGL-1 基因中的 Met62Ile SNP 与动脉粥样硬化风险之间的关联。本研究旨在分析该多态性与颈动脉粥样硬化程度和炎症及止血的生化标志物之间的可能关联。275 例因颈动脉狭窄>70%而行颈动脉内膜切除术的患者和 256 例具有相同种族起源的对照组被纳入研究。通过 PCR-RFLP 确定 Met62Ile 基因型。与其他基因型相比,Ile/Ile 纯合子患者的 CRP 明显更高。女性患者的颈动脉斑块存在与 Ile 等位基因剂量依赖性相关(Met/Met 与 Met/Ile 与 Ile/Ile;OR1,OR2.02,CI1.0-4.08,OR4.08,CI1.0-16.81,分别,p=0.04)。我们的结果表明 PSGL-1 Met62Ile 多态性对晚期动脉粥样硬化中的炎症有影响。我们观察到 Met62Ile 与晚期颈动脉粥样硬化之间存在性别差异的关联。在更大和不同人群中的研究应该验证并进一步检查 PSGL-1 中遗传变异与动脉粥样硬化和血栓形成的建议作用。