Norepinephrine transporter gene (NET) polymorphism in patients with type 2 diabetes.
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 > or =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).


CONCLUSIONS
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.
Ksiazek
Piotr
P
Laboratory for Molecular Diagnostics of Multifactorial Diseases, Department of Nephrology, Skubiszewski Medical University, Lublin, Poland.
Buraczynska
Kinga
K
Buraczynska
Monika
M
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic
D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D009638:Norepinephrine