Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients.
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.


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.


CONCLUSIONS
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.
Eto
Masaaki
M
Department of Medicine, Diabetes and Endocrine Division, Kawasaki Medical School, Kurashiki, Japan. eto@med.kawasaki-m.ac.jp
Saito
Mieko
M
Okada
Mizuho
M
Kume
Yoshie
Y
Kawasaki
Fumiko
F
Matsuda
Masafumi
M
Yoneda
Masaya
M
Matsuki
Michihiro
M
Takigami
Shigeru
S
Kaku
Kohei
K
D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
D001057:Apolipoproteins E; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol