Ha S K, Park H S, Kim K W, Kim S J, Kim D H, Kim J H, Lee H Y, Han D S
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Nephrol Dial Transplant. 1999 Sep;14(9):2144-9. doi: 10.1093/ndt/14.9.2144.
Apolipoprotein E (apo E) is known to play an important role in lipoprotein metabolism through its ability to bind to the receptors as a ligand. Three different apo E alleles (epsilon2, epsilon3 and epsilon4) produce six apo E genotypes (epsilon2/2, epsilon2/3, epsilon2/4, epsilon3/3, epsilon3/4 and epsilon4/4). The objective of this study was to investigate an association between apo E gene polymorphism and macroalbuminuria in 167 Korean patients with non-insulin dependent diabetes mellitus (NIDDM).
The patients in the macroalbuminuria group (n = 74) represent those in whom 24 h urinary albumin excretion was above 300 mg. The patients in the normoalbuminuria group (n = 93) represent those in whom 24 h urinary albumin excretion was below 30 mg and serum creatinine levels were less than 1.2 mg/dl. The duration of diabetes in all patients was at least 8 years.
There were no significant differences in terms of age, sex, body mass index, HbA1c, total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol between the two groups. In the macroalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 2 (2.7%), epsilon2/3 14 (18.9%), epsilon2/4 0 (0%), epsilon3/3 47 (63.5%), epsilon3/4 11 (14.9%) and epsilon4/4 0 (0%). In the normoalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 0 (0%), epsilon2/3 7 (7.5%), epsilon2/4 1 (1.1%), epsilon3/3 72 (77.4%), epsilon3/4 12 (12.9%) and epsilon4/4 1 (1.1%). There was no significant difference in the distribution of apo E genotypes between the two groups. However, there was a significant difference in the allele frequencies, epsilon2 frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (12.2% vs 4.3%, P<0.05). Also, we compared apo E carrier frequencies between the two groups. Epsilon2 carrier frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (21.6% vs 7.6%, P<0.05). In each group, there was no significant difference in the degree of lipid abnormalities between apo epsilon2 carrier (epsilon2/2, epsilon2/3 genotypes), epsilon3 carrier (epsilon3/3 genotype) and epsilon4 carrier (epsilon3/4, epsilon4/4 genotype).
Apo epsilon2 allele and epsilon2 carrier frequencies were significantly higher in macroalbuminuria group. These results suggest that epsilon2 allele may be associated with the development of clinical albuminuria in Korean patients with NIDDM.
载脂蛋白E（apo E）已知通过其作为配体与受体结合的能力在脂蛋白代谢中发挥重要作用。三种不同的apo E等位基因（ε2、ε3和ε4）产生六种apo E基因型（ε2/2、ε2/3、ε2/4、ε3/3、ε3/4和ε4/4）。本研究的目的是调查167例韩国非胰岛素依赖型糖尿病（NIDDM）患者中apo E基因多态性与大量白蛋白尿之间的关联。
大量白蛋白尿组（n = 74）的患者为24小时尿白蛋白排泄量高于300mg者。正常白蛋白尿组（n = 93）的患者为24小时尿白蛋白排泄量低于30mg且血清肌酐水平低于1.2mg/dl者。所有患者的糖尿病病程至少8年。
两组在年龄、性别、体重指数、糖化血红蛋白、总胆固醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇方面无显著差异。在大量白蛋白尿组中，apo E基因型分布为：ε2/2 2例（2.7%），ε2/3 14例（18.9%），ε2/4 0例（0%），ε3/3 47例（63.5%），ε3/4 11例（14.9%），ε4/4 0例（0%）。在正常白蛋白尿组中，apo E基因型分布为：ε2/2 0例（0%），ε2/3 7例（7.5%），ε2/4 1例（1.1%），ε3/3 72例（77.4%），ε3/4 12例（12.9%），ε4/4 1例（1.1%）。两组间apo E基因型分布无显著差异。然而，等位基因频率存在显著差异：大量白蛋白尿组的ε2频率显著高于正常白蛋白尿组（12.2%对4.3%，P<0.05）。此外，我们比较了两组间apo E携带者频率。大量白蛋白尿组的ε2携带者频率显著高于正常白蛋白尿组（21. — 6%对7.6%，P<0.05）。在每组中，ε2携带者（ε2/2、ε2/3基因型）、ε3携带者（ε3/3基因型）和ε4携带者（ε3/4、ε4/4基因型）之间的脂质异常程度无显著差异。
大量白蛋白尿组中apo ε2等位基因和ε2携带者频率显著更高。这些结果表明，ε2等位基因可能与韩国NIDDM患者临床白蛋白尿的发生有关。
