Influence of Apolipoprotein E Genotype on Progression of Diabetic Nephropathy

Abstract

Aims: Diabetic nephropathy progresses at a variable rate part of which may be explained by genetic polymorphisms. ApoE polymorphisms are associated with progression of atherosclerosis and because of the similarities between atherosclerosis and glomerulosclerosis, we chose to examine apoE and its role in progression of diabetic nephropathy. Methods: The apoE genotypes of 90 patients with type 2 diabetes and nephropathy who were recruited into a 2-year prospective randomised controlled study comparing intensive medical management with routine clinical care were analysed. The primary endpoint was the rate of progression of renal disease in the second year. Results: The apoE genotype frequencies were 49 with E3/3, 20 with E2/3, 17 with E3/4 and 4 with of E2/4. There were no significant differences in age, degree of renal failure, BP, albuminuria or glycaemic control between any genotype. The rate of progression of renal failure of patients with the E3/4 genotype was 0.80 ml/min/month compared to 0.30 ml/min/month for E2/3 and 0.18 ml/min/month for those with E3/3. Patients with E3/4 genotype had significantly faster rates of progression in the second year when compared with the other 3 genotypes (0.80 vs. 0.25 ml/min/month, p = 0.012). There was no difference in mortality according to apoE genotype. Conclusion: Patients who possess the apoE3/4 genotype had significantly faster rates of progression of renal failure.

Quantitative Trait Loci for Urinary Albumin in Crosses Between C57BL/6J and A/J Inbred Mice in the Presence and Absence of Apoe

“…Several human association studies have shown an association of APOE with renal damage parameters in different groups of patients (Werle et al 1998;Araki et al 2000;Joss et al 2005). Additionally, we found an association between serum APOE levels and albuminuria in the general population (R. Korstanje, unpublished data).…”

Association of the Angiotensinogen M235T and APO E Gene Polymorphisms in Turkish Type 2 Diabetic Patients with and without Nephropathy

“…However, the large number of studies into this issue has failed to reach a definitive conclusion. 1,6,13,15,42 As was the case in our study, several others also claim that carrying e2 allele may increase the risk for DN. For instance, Araki et al showed in their prospective study that the presence of e2 allele increased the risk for DN.…”

“…28,[38][39][40][41] APO E also plays a role in central and peripheral nerve regeneration, immunoregulation, cellular growth and differentiation, and recovery of tissue damage. 42 APO E is further claimed to decrease vascular smooth muscle cell proliferation capacity and increase vascular heparan sulfate proteoglycan level. 43 Elevated heparan sulfate proteoglycan levels inhibit mesangial cell proliferation and assist the formation of glomerular basal membrane and main filtration barrier in the interstitium.…”

“…On the other hand, some other studies found no relationship between APO E2 and DN. 6,42,45,46 Conversely, Boizel et al 47 claimed that the risk for DN was lower with APO E2 than it was with E3 and E4. In another study conducted with a Turkish population, Ilhan et al 31 claimed that there might be a relationship between APO E4 isoform and DN.…”

Relationship between apolipoprotein E gene polymorphism with triglyceride level in patients with renal diseases

“…Two studies 11,12 11,12,14 were recruited into the study of E2E4 versus E3E3 (including 4 comparisons). Twelve reports [11][12][13][14][15][16][17][18][19][20][21][22] were recruited into the study of E3E4 versus E3E3 (including 17 comparisons). Three reports 11,12,14 were recruited into the study of E4E4 versus E3E3 (including 4 comparisons).…”