Familial and epidemiological studies have indicated that there is a strong genetic component in the aetiology of diabetic nephropathy in Type I diabetes patients [1,2]. Apolipoprotein E (apoE) was discovered as a plasma protein involved in the metabolism of lipoproteins. Recently, the apolipoprotein E (APOE) gene has been suggested to be a risk factor for the development of micro- and macrovascular complications in diabetic patients.

The APOE gene is polymorphic. There are three common alleles, E2, E3, and E4, which code for three major isoforms, resulting in six common genotypes [3,4]. Individuals with apoE2 have higher triglyceride levels and are associated with lower cholesterol compared to individuals with apoE3. Individuals with apoE4 often have elevated plasma cholesterol levels. There is an increased prevalence of cardiovascular disease and particularly Alzheimer's disease [5,6,7].

Apolipoprotein E polymorphism may influence the metabolism of lipoproteins in diabetic patients. Several recent studies have suggested that this polymorphism may be associated with a genetic predisposition for diabetic nephropathy [8,9,10,11]. Thus, APOE is an important candidate gene for the development of microvascular complications in Type I diabetes patients.

The aim of this study was to investigate the influence of APOE gene polymorphism in the development of diabetic nephropathy and retinopathy in Type I diabetes patients.

Clinical characteristics by study group are shown in Table 1. No significant difference was seen between groups with vascular complications (nephropathy and retinopathy) and those without, no matter the age, diabetes duration, age at diabetes onset, and mean HbAlc.

The frequency of each genotype in each group conformed to the Hardy -Weinberg equilibrium.

The distribution of the APOE genotypes is shown in Table 2. There was no significant difference in APOE genotype and allele frequency between nephropathic and normoalbuminuric diabetic patients. In this study, no association was found between diabetic retinopathy and APOE polymorphisms. APOE allele frequencies for males and females were similar within groups and in different groups.

Diabetic nephropathy and diabetic retinopathy are the two most important microangiopathic complications in Type I diabetic patients. Many of the environmental factors that influence the risk of vascular disease are known, but genetic components of the risk for diabetic microangiopathy are poorly understood. Several candidate genes have been investigated to elucidate the genetic factors responsible for vascular complications. The most important of these are the aldose reductase gene (ALR2) [17], the insertion/deletion (I/D) polymorphism of the angiotensin I – converting enzyme (ACE) gene [18,19], C825T polymorphism of the gene encoding the beta-3 subunit of geterotrimeric G-proteins (GNB3) [20,21,22], and C677T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR) [23].

The genetic polymorphism of apolipoprotein E is associated with lipid abnormalities. Eto et al. [9] suggested that lipid abnormalities may contribute to the development and progression of kidney disease, including diabetic nephropathy. The E2 allele frequency was significantly higher in Type II diabetes patients with nephropathy (7.2%) and with renal failure (9.7%) than in diabetic patients without nephropathy (2.6%) [9]. Apolipoprotein E polymorphism is associated with the progression of diabetic nephropathy. Presence of the apolipoprotein E4 allele is a protective factor, and other alleles entail risk factors [24].

The genes responsible for genetic predisposition to vascular complications are still unknown, and little is known about the molecular basis of these complications. The influence of the APOE gene polymorphism to the development of diabetic microangiopathy is uncertain. Chowdhury et al. [10] and Araki et al. [11] demonstrated an association between the presence of the APOE E2 allele and diabetic nephropathy in Caucasian patients with Type I diabetes, although some investigators do not support this association [25,26].

This study elucidated the role of APOE gene polymorphism in the predisposition to diabetic vascular complications. No association ofAPOE gene polymorphism with diabetic nephropathy was demonstrated. This result for diabetic nephropathy confirms the findings of Tarnow et al. [25] and Onuma et al. [26]. It should be mentioned that sample sizes in [10,11] were larger than in this study. With increased sample size comes the possibility to demonstrate an association. But the larger the necessary and sufficient minimal sample size, the weaker the association demonstrated.

We also analysed the association of the APOE gene polymorphism with diabetic retinopathy in the present study. No significant differences were found between groups with and without this vascular complication. A similar result has been shown by Tarnow et al. [25] for diabetic retinopathy.

The present study found no evidence for a role of the APOE gene polymorphism in genetic susceptibility for the development of diabetic retinopathy in Type I diabetes patients. Association between APOE gene polymorphism and diabetic nephropathy may be weak or moderate, but not strong.

None declared.