Norepinephrine Transporter Gene (NET) Polymorphism in Patients with Type 2 Diabetes

Abstract

Background: Norepinephrine transporter (NET) is involved in the regulation of norepinephrine (NE) turnover and metabolism. Neuronal NE reuptake may be impaired in individuals with renal disease and/or hypertension due to dysfunction of the NE transporter. A silent G1287A nucleotide substitution in exon 9 of the NET gene was studied in human conditions involving hypertension. We investigated its effect in patients with type 2 diabetes. Methods: The study involved 215 type 2 diabetes patients with nephropathy, 95 patients with diabetes duration ≧10 years, free of nephropathy, and 360 healthy subjects. All individuals were genotyped for the NET-8 gene polymorphism with the PCR-RFLP method. Genotype and allele frequencies were compared between the groups. NE was measured by high-performance liquid chromatography and electrochemical detection. Results: We genotyped 310 patients and 360 controls for the NET gene polymorphism. Genotype distribution in both groups was in accordance with the Hardy-Weinberg equilibrium. There were no significant differences in the frequency of genotypes and alleles between patients and controls (p = 0.43). The frequencies were also similar for patients with nephropathy and those without. After dividing the patient group into hypertensive (n = 208) and normotensive (n = 102) subjects, there was a significant increase in the frequency of the AA genotype in patients with hypertension compared to normotensives (19 vs. 10%, p < 0.05). Conclusion: No association was found between G1287A polymorphism in the NET gene and diabetes. Our results suggest that this polymorphism has a possible role in increased susceptibility to hypertension in patients with type 2 diabetes.