Campo Salvatore, Sardo Maria A, Bitto Alessandra, Bonaiuto Antonio, Trimarchi Giuseppe, Bonaiuto Michele, Castaldo Maria, Saitta Carlo, Cristadoro Simona, Saitta Antonino
Department of Internal Medicine and Institute of Statistical Science, School of Medicine, University of Messina, Messina, Italy.
Clin Chem. 2004 Nov;50(11):2077-82. doi: 10.1373/clinchem.2004.036863. Epub 2004 Sep 13.
Atherosclerosis is a complex, chronic disease that usually arises from the converging action of several pathogenic processes, including hypertension, hyperlipidemia, obesity, and the accumulation of oxidized LDL. Platelet-activating factor acetylhydrolase (PAF-AH) is a LDL- and HDL-bound enzyme that hydrolyzes and inactivates PAF and prevents LDL-cholesterol oxidation, thus delaying the onset of atherosclerotic disease.
We evaluated the relationship between variants of the PAF-AH gene polymorphisms Arg92His, Ile198Thr, and Ala379Val and the presence of carotid atherosclerosis in 190 hypercholesterolemic Sicilian individuals. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The participants were classified according to having normal (< or =1 mm) or abnormal (> or =1 mm) IMT and were also investigated for physical characteristics and biochemical indices, including PAF-AH activity.
PAF-AH activity and LDL concentrations were significantly correlated in hypercholesterolemic patients, but plasma PAF-AH activity and HDL were not significantly correlated in either IMT group. No significant differences were detected among the PAF-AH gene polymorphisms in both groups after correction for age, sex, body mass index, plasma glucose and lipid concentrations, PAF-AH activity, blood pressure, and smoking habits. The analysis of PAF-AH genotype distribution showed no significant differences in percentage of 92, 198, and 379 genotypes in both IMT groups.
Our data provided no evidence that PAF-AH polymorphisms influence PAF-AH activity and atherosclerosis in hypercholesterolemic Sicilian patients.
动脉粥样硬化是一种复杂的慢性疾病,通常由多种致病过程共同作用引起,包括高血压、高脂血症、肥胖以及氧化型低密度脂蛋白(LDL)的积累。血小板活化因子乙酰水解酶(PAF-AH)是一种与LDL和高密度脂蛋白(HDL)结合的酶,它能水解并使PAF失活,防止LDL胆固醇氧化,从而延缓动脉粥样硬化疾病的发生。
我们评估了PAF-AH基因多态性Arg92His、Ile198Thr和Ala379Val的变异与190名西西里高胆固醇血症患者颈动脉粥样硬化之间的关系。测量颈动脉内膜中层厚度(IMT)作为早期动脉粥样硬化疾病的指标。根据IMT正常(≤1mm)或异常(≥1mm)对参与者进行分类,并对其身体特征和生化指标进行研究,包括PAF-AH活性。
在高胆固醇血症患者中,PAF-AH活性与LDL浓度显著相关,但在两个IMT组中,血浆PAF-AH活性与HDL均无显著相关性。在校正年龄、性别、体重指数、血糖和血脂浓度、PAF-AH活性、血压和吸烟习惯后,两组PAF-AH基因多态性之间未检测到显著差异。PAF-AH基因型分布分析显示,两个IMT组中92、198和379基因型的百分比无显著差异。
我们的数据没有提供证据表明PAF-AH基因多态性会影响西西里高胆固醇血症患者的PAF-AH活性和动脉粥样硬化。