Apolipoprotein E Polymorphism and the Progression of Diabetic Nephropathy in Type 2 Diabetes

Abstract

Background/Aims: Three different apo E alleles (E2, E3 and E4) produce apo E isoproteins, which regulate the metabolism of lipoproteins. This study investigated the apo E polymorphisms as a prognostic factor for the development of diabetic nephropathy (DN). Methods: A total of 525 type 2 diabetic patients were enrolled to participate in this prospective observational study. Apo E gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study. Results: The mean follow-up period was 42.4 months. The patients whose DN progressed had significantly higher urine albumin/creatinine ratios and fewer used diuretics than those in whom DN did not progress. In the Cox regression analysis, the apo E4 carriers were found to be at greater risk of progression of DN than non-apo E4 carriers (p = 0.007, hazard ratio 2.252). After adjusting for confounding factors, apo E4 carriers remained at increased risk of progression to more severe DN (p = 0.002, hazard ratio 2.820). Conclusion: Our study suggests the apo E4 carrier might serve as a predictor of DN progression in Taiwan.

The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis

“…All statistical analyses were performed with STATA Statistical Package (version 10.0) and were 2 sided, with a significance level of P < 0.05. [14,24,31]. Three sub-studies from one paper about PPARγ rs1801282 C>G polymorphism and 10 sub-studies from two articles about ACACB polymorphism were treated as separate studies in our analyses given that the study bases were sampled from different geographical locations or belonged to different ethnicities.…”

“…Twenty publications were carried out in Asians [2-4, 6, 8-10, 13, 14, 19, 22, 26, 31, 34, 36-38, 42-44], 12 in Caucasians [12,17,18,20,21,23,32,33,35,[39][40][41], and 1 in mixed populations [11]. Ten studies reported on microalbuminuria [10,12,14,19,21,22,35,37,40,41], seven reported on macroalbuminuria [6,14,17,19,21,37,41], whereas only three studies were about ESRD [25]. Examining genotype frequencies in the controls, significant deviation from HWE was detected in the four studies [3,4,33,34].…”

“…Most of them supported that ApoE ε2 might be a risk factor for T2DN [6,8,9], and individuals with the ε4 genotype had a decreased risk of T2DN [10,11]. But Erdogan et al reported that ApoE gene polymorphism was not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients [12], and two larger prospective studies also did not detect the relationship between ApoE ε2 and T2DN; what's more, Tien et al found that ApoE ε4 carrier was at great risk of progression of T2DN [13,14].…”

APOE polymorphism and diabetic nephropathy

“…On the other hand, some follow-up studies have reported no association between the e2 allele and DN progression [24,25]. However, we need to interpret the results of these studies carefully.…”

“…This study analyzed only 169 diabetic patients with normoalbuminuria at the 4-year follow-up, which may lack the power to detect the significance of the e2 allele. In addition, Tien et al [25] investigated 525 patients with type 2 diabetes in a prospective observational study with a median follow-up of 42.4 months. However, this study included diabetic patients with overt proteinuria, and DN progression in those with overt proteinuria was defined as the doubling of serum creatinine instead of the shift to the higher stage of albuminuria that is used in those with normoalbuminuria and microalbuminuria.…”