Endocrine Abstracts

Introduction and Aim: Dopamine receptor D2 (DRD2) polymorphism (rs1800497) appears to be associated with increased susceptibility to the development of type 2 diabetes mellitus (T2DM). The dopamine transporter (DAT) determines dopamine signalling, responsible for the reuptake of its active form from the synapse. Polymorphism in the DAT gene (rs2836317) can increase dopamine reuptake in the synaptic cleft. However, its association with T2DM is still controversial.

This study aimed to evaluate the relationship between genetic polymorphisms of DAT and DRD2 and the susceptibility to the development of angiopathy in T2DM and its influence on the biochemical parameters.

Design and Methods: 150 patients with T2DM were divided into: G1-75 patients with angiopathy and G2-75 patients without angiopathy. The DRD2 and DAT polymorphism were determined by endpoint analysis method and PCR, respectively. Blood levels of malondialdehyde (MAD), ascorbic acid, homocysteine and cysteine, vitamins B6 (vit.B6), B12 (vit.B12) were measured by HPLC methods, and standardized methods determined the other biochemical parameters. Statistical analysis was performed using SPSS with statistical significance for P<0.05.

Results: There were differences only in the DRD2 polymorphism between G1 to G2 (P=0.016). Carriers of allele A of DRD2 had a 3.18-fold increased risk to angiopathy (OR=3.18 [1.40-7.21], P=0.006). Analyzing the relationship of biochemical parameters between groups was found an increase in systolic blood pressure (SBP) (P=0.023), MAD (P=0.010) and retinol (P=0.011) in G1. Regarding DRD2 polymorphism, there was an increase in HDL cholesterol (HDL-C) (P=0.035) for genotype GG and of vit.B12 in carriers of the allele G (P=0.013). For DAT polymorphism, it was found an increase in weight (P=0.042) and waist circumference (P=0.050) and a decrease in ascorbic acid (P=0.039) for genotype 10/10 and an increase in LDL cholesterol (LDL-C) (P=0.027) in genotype 9/10. Biochemical parameters were compared between groups, but dividing the population by the studies polymorphisms, for DAT it was found higher values of SBP (P=0.014), triglycerides (P=0.019) and retinol (P=0.031) and lower HDL-C values (P=0.050) for carriers of allele 10 in G1; for DRD2 it was found in carriers of the allele A, higher values of homocysteine (P=0.038), cysteine (P=0.035) and retinol (P=0.007) and in the genotype GG higher values of SBP (P=0.020) and triglycerides (P=0.011) in G1.

Conclusions: DRD2 polymorphism appears to influence susceptibility to angiopathy in T2DM patients directly. DAT and DRD2 polymorphism may modulate disease-associated biochemical parameters.