Diabetic nephropathy and apolipoprotein E2 allele

糖尿病肾病与载脂蛋白E2等位基因

基本信息

批准号：
12671128
负责人：
ETO Masaaki
金额：
$ 1.6万
依托单位：
KAWASAKI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

以前，我们证明了载脂蛋白（APO）E E2等位基因与糖尿病肾病的进展有关。本研究的目的是进一步研究Apo e遗传多态性，血浆残留脂蛋白和糖尿病性肾病之间的关联。一百五十八名2型糖尿病患者在10年内糖尿病持续时间分为3个APO E组。测量了Apo E2，E3/3和E4。脂质和残留脂蛋白的铂水平是测量的。ApoE2 E2甘油三酸酯（TG） - 富含脂蛋白（包括残留脂蛋白）对通过人膜细胞（HMCS）估算胆汁脂蛋白积累的富含脂蛋白的影响（HMCS）的影响刺激14c-Oleate掺入胆固醇酯中。 APO E2糖尿病患者（59.1％）明显的明显肾病的频率比APO E3/3（34.3％）或APO E4患者（8％）（8％）高，而Normoalbuminuria的频率明显高于APO E4糖尿病患者（67 6％）比APO E3/3（34.3％）或APO E2患者（4.5％）。后勤回归分析表明，对于明显的肾病的存在的APO E2和APO E4基因型的优势比分别为10.179（P = 00349）和0.129（P = 0.0028）。血浆甘油三酸酯和残留样脂蛋白颗粒（RLP） - 胆碱的水平明显更高，而NAPO E4患者明显低于APO E3/3患者。富含APO E2 TG的脂蛋白刺激HMC刺激胆固醇酯的积累，其高于APO E3/3或APO E4 TG富含脂蛋白。 APO E2，S阳性遗传因子和Apo E4是糖尿病性肾病的负遗传因子。 HMCS更加狂热地吸收了富含APO E2 TG TG的脂蛋白。残留的脂蛋白可能在糖尿病肾病的进展中起重要作用。