Background: The serotonergic system contributes substantially to the regulation of glucose homeostasis and feeding. 5-HTTLPR is a serotonin transporter (5-HTT) gene-linked polymorphic region that regulates the transcriptional activity of 5-HTT. Our aim was to investigate the possible association of 5-HTTLPR polymorphism with type 2 diabetes mellitus and obesity.
Methods: Study population consisted of 252 subjects diagnosed with Type 2 DM and 211 non-diabetic subjects, all Caucasians of Greek ethnic origin. Genomic DNA was extracted from peripheral blood and analyzed for 5-HTTLPR polymorphism with a novel PCR protocol.
Results: The frequency of SS and SL genotypes of HTTLPR was significantly higher in the diabetic group (77.0%) than in the non-diabetic group (61.6%) (P<0.001). The genetic risk of Type 2 DM for subjects carrying at least one S allele was increased compared to non-diabetic subjects (OR=2.08, 95% CI=1.39-3.12). When subjects were divided according to BMI status, the frequency of S allele carriers was similar in obese and non-obese subjects.
Conclusions: The S allele of 5-HTTLPR is strongly associated with the presence of Type 2 DM. This association appears to be direct and not dependent on obesity status. Therefore, 5-HTTLPR LL genotype might be protective for development of Type 2 DM.
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