Apolipoprotein E gene polymorphism in renal transplant recipients:: effects on lipid metabolism, atherosclerosis and allograft function
Apolipoprotein E gene polymorphism in renal transplant recipients:: effects on lipid metabolism, atherosclerosis and allograft function
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DOI：
10.1111/j.1399-0012.2004.00162.x
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发表时间：
2004-06-01
影响因子：
2.1
通讯作者：
Çaglar, S
中科院分区：
文献类型：
--
作者：
Kahraman, S;Kiykim, AA;Çaglar, S
引言：动脉粥样硬化是肾移植受者（RTRs）的严重并发症和主要死亡原因。高血压可能与肾脏疾病的进展和慢性移植物功能障碍有关。肾小球硬化和动脉粥样硬化的发病机制相似。载脂蛋白（载脂蛋白）E基因编码形成三个主要的异构体（E2，E3，和E4）与变量的影响，对脂质metabolic.Patients和方法：共118例患者，平均年龄为40 +/- 8岁，包括在研究中。采用聚合酶链反应和限制性内切酶对基因组DNA进行载脂蛋白E基因分型。B超检测颈动脉内膜、中层厚度及粥样硬化斑块。还研究了脂质和脂蛋白以及急性期反应物的血浆水平。结果：E2、E3和E4等位基因频率分别为0.10、0.78和0.12。25%的E2携带者、30%的E3携带者和57%的E4携带者存在颈动脉粥样硬化。载脂蛋白E4携带者的总胆固醇、总甘油三酯、低密度脂蛋白、极低密度脂蛋白、载脂蛋白B 100水平较高。载脂蛋白E2携带者的中位载脂蛋白A1水平更高，同种异体移植物功能更好（p < 0.05）。多元回归分析显示，移植物功能与急性期反应物升高呈负相关（p < 0.01），只有年龄是动脉粥样硬化性血管疾病的独立危险因素，而apoE基因型不是（p < 0.01）。结果表明，载脂蛋白E基因型对移植肾的血脂、脂蛋白及移植肾功能均有影响.载脂蛋白E4基因多态性作为RTRs中动脉粥样硬化发生和发展的危险因素的最终作用有待进一步研究。
Introduction: Atherosclerosis is a serious complication and leading cause of mortality in renal transplant recipients (RTRs). Hyperlipidemia may be associated with progression of renal disease and chronic allograft dysfunction. Similarities in the pathogenesis of glomerulosclerosis and atherosclerosis have been proposed. Apolipoprotein (apo) E gene code forms three major isoforms (E2, E3, and E4) with variable effects on lipid metabolism.Patients and Methods: A total of 118 patients, at a mean age of 40 +/- 8 yr, were included in the study. Apo E genotyping was carried out on genomic DNA using polymerase chain reaction and restriction enzyme. Carotid artery intima media thickness and atherosclerotic plaques were evaluated by B-mode ultrasonography. The plasma levels of lipids and lipoproteins and acute phase reactants were also studied. Allograft function was evaluated by measuring serum creatinine and creatinine clearance values.Results: The frequencies of E2, E3, and E4 alleles were 0.10, 0.78, and 0.12 respectively. Carotid artery atherosclerosis was found in 25% of E2 carriers, 30% of E3 carriers, and 57% of E4 carriers. Total cholesterol, total triglyceride, low-density lipoprotein, very low-density lipoprotein, apo B 100 levels were found to be higher in apo E4 carriers. Median apo A1 level was higher and allograft functions were better in apo E2 carriers (p < 0.05). Multiple regression analysis showed that allograft functions were negatively correlated with elevated acute phase reactants (p < 0.01) and only the age, but not the apo E genotypes, was an independent risk factor for atherosclerotic vascular disease (p < 0.01).Discussion: The pathogenetic events linking lipid metabolism and allograft functions and development of atherosclerosis are complex and multifactorial in RTRs. Our results showed that apo E genotypes have influences on lipids, lipoproteins and allograft functions. The ultimate role of apo E4 gene polymorphism as a risk factor for development and progression of atherosclerosis in RTRs should be sought in further studies.