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Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients
Masaaki Eto1, Mieko Saito, Mizuho Okada
1Department of Medicine, Diabetes and Endocrine Division, Kawasaki Medical School, Kurashiki, Japan. eto@med.kawasaki-m.ac.jp
Background:
We previously showed that the apolipoprotein (apo) Eepsilon2 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 lipid levels (particularly remnant lipoproteins), and diabetic nephropathy.
Subjects And Methods:
One hundred fifty-eight patients with type 2 diabetes who had a duration of diabetes longer than 10 years were divided into the three apo E groups: apo E2 (n = 22), E3/3 (n = 102), and E4 (n = 34). Plasma levels of lipids and remnant lipoproteins were measured. The effect of apo E2 triglyceride (TG)-rich lipoproteins, including remnant lipoproteins, on the accumulation of cholesteryl esters by human mesangial cells (HMCs) was estimated by measuring the stimulation of radioactive carbon-labeled oleate incorporation into cholesteryl esters.
Results:
The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (59.1%) than apo E3/3 (34.3%) or apo E4 patients (8.8%), and the frequency of normoalbuminuria was significantly greater in apo E4 patients with diabetes (67.6%) than 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 = 0.0349) and 0.129 (P = 0.0028), respectively. Plasma TG and remnant-like lipoprotein particle cholesterol levels were significantly greater in apo E2 patients and significantly lower in apo E4 patients than apo E3/3 patients. Apo E2 TG-rich lipoproteins stimulated the accumulation of cholesteryl esters by HMCs significantly more than apo E3/3 or apo E4 TG-rich lipoproteins.
Conclusion:
Apo E2 is a positive factor and apo E4 is a negative factor for diabetic nephropathy. Apo E2 TG-rich lipoproteins, including remnant lipoproteins, affected HMCs. Remnant lipoproteins may have an important role in the progression of diabetic nephropathy.