Diabetic nephropathy and apolipoprotein E2 allele

先前我们证实载脂蛋白ee2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、血浆残馀脂蛋白与糖尿病肾病的关系。158例糖尿病病程超过10年的2型糖尿病患者被分为3组载脂蛋白E；载脂蛋白E2 E3/3和E4。测定血脂和残余脂蛋白的血浆水平。通过测量14c -油酸酯掺入胆固醇酯的刺激，估计了载脂蛋白E2甘油三酯（TG）富含脂蛋白（包括残余脂蛋白）对人系膜细胞（HMCs）积累胆固醇酯的影响。apo E2糖尿病患者显性肾病发生率（59.1%）显著高于apo E3/3（34.3%）或apo E4 (8.8%)， apo E4糖尿病患者正常蛋白尿发生率（67.6%）显著高于apo E3/3（34.3%）或apo E2（4.5%）。logistic回归分析显示，apo E2和apo E4基因型与显性肾病的比值比分别为10.179 （p=00349）和0.129 （p=0.0028）。apo E2患者血浆中甘油三酯和残留物样脂蛋白颗粒(RLP)-胆固醇和水平显著高于apo E3/3患者，apo E4患者血浆中甘油三酯和残留物样脂蛋白颗粒(RLP)-胆固醇和水平显著低于apo E3/3患者。富含载脂蛋白E2 tg的脂蛋白比富含载脂蛋白E3/3或载脂蛋白E4 tg的脂蛋白更能刺激hmc积累胆固醇酯。载脂蛋白E2是糖尿病肾病的阳性遗传因素，而载脂蛋白E4是糖尿病肾病的阴性遗传因素。富含Apo E2 tg的脂蛋白在hmc中摄取较多。残馀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.