The -759C/T polymorphism of the 5-HT2C receptor is associated with type 2 diabetes in male and female Caucasians.

Objectives: Type 2 diabetes mellitus and obesity constitute serious health problems. Studies reveal that the 5-HT2C receptor contributes substantially to the regulation of a wide variety of behavioral and physiological processes including feeding and glucose homeostasis. Our aim was to determine the possible association of the -759C/T polymorphism of the 5-HT2C receptor gene with type 2 diabetes and obesity in male and female individuals Caucasian origin.

Methods: The study population consisted of 151 patients diagnosed with type 2 diabetes and 164 nondiabetic patients, all of Greek origin. Genomic DNA was extracted from peripheral blood and analyzed for the -759C/T polymorphism of the 5-HT2C receptor gene using polymerase chain reaction-restriction fragment length polymorphism method.

Results: The frequency of T allele of the -759C/T polymorphism of the 5-HT2C receptor was significantly lower in the diabetic group (12.6%) than in the nondiabetic group (23.3%) (P=0.003). The genetic risk of type 2 diabetes for patients not carrying the T allele was increased compared with nondiabetic patients (odds ratio (OR)=2.34, 95% confidence interval (CI)=1.36-4.02). The reduced frequency of T allele was present both in male [10% in patients with diabetes and 21.6% in patients without diabetes (P=0.041)] and female patients [14.1% in patients with diabetes and 24.3% in patients without diabetes (P=0.030)]. In contrast, the frequency of T allele was similar in obese (16.4%) and nonobese (17.1%) patients.

Conclusions: Lower frequency of -759T allele of the 5- HT2C receptor gene was associated with type 2 diabetes but not with obesity in male and female Caucasians. Thus, this polymorphism might constitute a prognostic marker for diabetic risk.