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 (ε2, ε3 and ε4 produce six apo E genotypes (ε2/2, ε2/3, ε2/4, ε3/3, ε3/4 and ε4/4). 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, HbA1c, total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol between the two groups. In the macroalbuminuria group, the distribution of apo E genotypes revealed ε2/2 2 (2.7%), ε2/3 14 (18.9%), ε2/4 0 (0%), ε3/3 47 (63.5%), ε3/4 11 (14.9%) and ε4/4 0 (0%). In the normoalbuminuria group, the distribution of apo E genotypes revealed ε2/2 0 (0%), ε2/3 7 (7.5%), ε2/4 1 (1.1%), ε3/3 72 (77.4%), ε3/4 12 (12.9%) and ε4/4 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, ε2 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. ε2 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 ε2 carrier (ε2/2, ε2/3 genotypes), ε3 carrier (ε3/3 genotype) and ε4 carrier (ε3/4, ε4/4 genotype). Conclusion. Apo ε2 allele and ε2 carrier frequencies were significantly higher in macroalbuminuria group. These results suggest that ε2 allele may be associated with the development of clinical albuminuria in Korean patients with NIDDM.