Diabetic nephropathy and apolipoprotein E2 allele

以前我们证明载脂蛋白（apo）E e2等位基因与糖尿病肾病的进展有关。本研究旨在进一步探讨载脂蛋白E基因多态性和血浆残余脂蛋白与糖尿病肾病的关系。将158例糖尿病病程10年以上的2型糖尿病患者分为3组，分别为apo E组、apo E组、apo E组和apo E组。载脂蛋白E2，E3/3和E4.测定血浆脂质和残余脂蛋白水平，探讨富含载脂蛋白E2的甘油三酯（TG）脂蛋白（包括残余脂蛋白）对人肾小球系膜细胞（HMCs）胆固醇酯蓄积的影响。通过测量14 C-油酸酯掺入胆固醇酯的刺激来估计。载脂蛋白E2型糖尿病患者的显性肾病发生率（59.1%）明显高于载脂蛋白E3/3型（34.3%）和载脂蛋白E4型糖尿病患者（8.8%）;载脂蛋白E4型糖尿病患者的正常白蛋白尿发生率（67.6%）明显高于载脂蛋白E3/3型（34.3%）和载脂蛋白E2型（4.5%）。对数回归分析显示，载脂蛋白E2和载脂蛋白E4基因型与显性肾病的比值比分别为10.179（p= 0.00349）和0.129（p=0.0028）。与apo E3/3患者相比，apo E2患者的血浆甘油三酯和残粒样脂蛋白颗粒（RLP）-chol水平显著较高，apo E4患者的血浆甘油三酯和残粒样脂蛋白颗粒（RLP）-chol水平显著较低。载脂蛋白E2富TG的脂蛋白比载脂蛋白E3/3或载脂蛋白E4富TG的脂蛋白更能促进HMCs胆固醇酯的积累。载脂蛋白E2是糖尿病肾病的阳性遗传因子，载脂蛋白E4是糖尿病肾病的阴性遗传因子。载脂蛋白E2 TG丰富的脂蛋白被HMCs更贪婪地摄取。残余脂蛋白可能在糖尿病肾病的进展中起重要作用。

Previously we demonstrated that the apolipoprotein (apo) E e2 allele is associated with the progression of diabetic nephropathy. The aim of the present study is to further investigate the association between apo E genetic polymorphism, plasma remnant lipoproteins and diabetic nephropathy. One hundred and fifty eight type 2 diabetic patients who had a diabetes duration over 10 years were divided into the 3 apo E groups ; apo E2, E3/3 and E4.Plasma levels of lipids and remnant lipoproteins were measured.The effect of apo E2 triglyceride (TG)-rich lipoproteins including remnant lipoproteins on accumulation of cholesteryl esters by human mesangial cells (HMCs) was estimated by measurement of the stimulation of 14C-oleate incorporation into cholesteryl esters. The frequency of overt nephropathy was significant^ higher in apo E2 diabetic patients (59.1%) than in apo E3/3 (34.3%) or apo E4 patients (8 8%) and the frequency of normoalbuminuria was significantly higher in apo E4 diabetic patients (67 6%) than in apo E3/3 (34.3%) or apo E2 patients (4.5%). Logistical regression analysis showed that odds ratios of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 10.179 (p=00349) and 0.129 (p=0.0028), respectively. Plasma levels of triglyceride and remnant-like lipoprotein particles (RLP)-chol and were significantly higher in apo E2 patients, and significantly lower, n apo E4 patients than in apo E3/3 patients. Apo E2 TG-rich lipoproteins stimulated accumulate of cholesteryl esters by HMCs significantly more than apo E3/3 or apo E4 TG-rich lipoproteins. Apo E2, s a positive genetic factor and apo E4 is a negative genetic factor for diabetic nephropathy. Apo E2 TG-rich lipoproteins were uptaken more avidly by HMCs. Remnant lipoproteins may have an important role in the progression of diabetic nephropathy.