Association between apolipoprotein E polymorphism and macroalbuminuria in patients with non-insulin dependent diabetes mellitus

Objectives. 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 (epsilon 2, epsilon 3 and epsilon 4) produce six apo E genotypes (epsilon 2/2, epsilon 2/3, epsilon 2/4, epsilon 3/3, epsilon 3/4 and epsilon 4/4). 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). Methods. 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. Results. There were no significant differences in terms of age, sex, body mass index, HbA(1c), total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol between the two groups. In the macroalbuminuria group, the distribution of apo E genotypes revealed epsilon 2/2 2 (2.7%), epsilon 2/3 14 (18.9%), epsilon 2/4 0 (0%), epsilon 3/3 47 (63.5%), epsilon 3/4 11 (14.9%) and epsilon 4/4 0 (0%). In the normoalbuminuria group, the distribution of apo E genotypes revealed epsilon 2/2 0 (0%), epsilon 2/3 7 (7.5%), epsilon 2/4 1 (1.1%), epsilon 3/3 72 (77.4%), epsilon 3/4 12 (12.9%) and epsilon 4/4 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, epsilon 2 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. epsilon 2 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 epsilon 2 carrier (epsilon 2/2, epsilon 2/3 genotypes), epsilon 3 carrier (epsilon 3/3 genotype) and epsilon 4 carrier (epsilon 3/4, epsilon 4/4 genotype). Conclusion. Apo epsilon 2 allele and epsilon 2 carrier frequencies were significantly higher in macroalbuminuria group. These results suggest that epsilon 2 allele may be associated with the development of clinical albuminuria in Korean patients with NIDDM.