Diabetic nephropathy and apolipoprotein E2 allele

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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.