Association Between The Serotonin Transporter Promoter Polymorphisms (5-HTTLPR) And Type 2 Diabetes Mellitus

Research backgrounds The incidences of mental illnesses in diabetic patients are very high, especially in the diabetic patients with depression. According to the World Health Organization data showed: the prevalence of depression worldwide is about 3%, And the prevalence of depression in diabetic patients is up to 33%.British scholar found that major depression may increase the incidence of type 2 diabetes in a retrosp -ective study. A number of studies have confirmed that emotional stress reaction can directly affect the function of the pancreas through physiological mechanisms including autonomic pathways, neuroendocrine mechanisms, vagus nerve, to induce diabetes or accelerate the progress of diabetes. Long-term endocrine disorders and the state of high stress in diabetic patients and increasing of various stress factors and strength may adversely increase the prevalence of depression or worsening depression. In recent years, a large number of studies have shown that antidepressant intervention was beneficial to blood glucose control in diabetic patients with depression, even hypoglycemia reported; And a good blood glucose control can reduce depression in diabetic patients. All these suggest a possible biological links between diabetes and depression, rather than two separate diseases, also suggested that neuroendocrine system may play an important role in the regulation of blood glucose. Depression was mainly due to 5-Hydroxytryptamine (5-HT) (hypothesis) and norepinephrine (hypothesis) dysfunction, Its main clinical manifestations were low depression, retardation, bulesis decreased and somatization. Earlier studies confirmed that 5-HT was stored together with insulin in their secretoryβ-granules, and it is co-released in the form of exocytosis when pancreatic islets are stimulated with glucose. 5-HT is an important neurotransmitter in vivo, recently, researches indicated 5-HT plays an important role in maintaining the glucose homeostasis, and the other researches suggested it might be associated with obesity, diabetes mellitus and its complications, drug dependence and Cardio Vascular Diseases. Serotonin transporter protein (serotonin transporter,5-HTT/SERT) is the main transporter of 5-HT, and play an important role in regulation of 5-HT physiological functions. 5-HTTLPR (serotonin transporter gene linked polymorphic region) can influence the physiological functions of 5-HT by regulating the expression of SERT protein and transcriptional activity. Many studies have shown that 5-HTTLPR was strong association with psychiatric disorders, especially depression. Some scholars even call it "depressive gene". Inspired from above theories, researchers guess 5-HTTLPR may also affect glucose metabolism. Follow-up studies have also shown 5-HTTLPR was associated with obesity, appetite, diabetes and its vascular complications. Based on the above researches, our study will investigate the distribution of 5-HTTLPR gene polymorphism in type 2 diabetes of Shandong Han Population, and may provide etiology evidence of type 2 diabetes of chinese population, also provide theoretical basis for studying diabetes neuroendocrine, as well as the treatment of type 2 diabetes or diabetes with depression.Objective To investigate the allele and the genotypic frequency distributions of the 5-HTTLPR gene in Shandong Han Population. To study the relationship between 5-HTTLPR gene and type 2 diabetes mellitus.Methods In this study, we selected 387 patients with type 2 diabetes and 286 healthy control individuals. All of the subjects are Shandong Han population.The technique of PCR were used to detected the polymorphism of 5-HTTLPR gene in 387 patients with type 2 diabetes mellitus (case group) and 286 healthy control individuals (control group),and the frequencies of allele and genotype were compared between the two groups. All subjects measured blood pressure, blood sugar, blood lipids, body mass index, liver and kidney function, compared differences in clinical parameters between the two groups. Results 1.Case group and control group are tested by independent samples T-test. Significant differences were found in body mass index, systolic blood pressure, triglyceride, low density lipoprotein cholesterol, fasting blood glucose, 2-hour postprandial blood glucose, blood urea nitrogen, blood uric acid.The other clinical parameters have no significant differences between the two groups. 2.The genotype frequencies of all subjects were consistent with Hardy-Weinberg equilibrium(χ~2=2.508, p>0.05),the samples are group representation. 3. Statistically significant were found in the three genotypic frequency distributions of 5-HTTLPR between the cases and the controls(χ~2=10.118, p<0.01),as well as the allele frequency distributions(χ~2=5.644, p<0.05);When subjects were divided according to caring at least one S allele(LS+SS), we found that this difference was statistically significant; but when according to L allele(LL+LS),no significant differences were found(χ~2=0.316, p>0.05). 4.Logistic regression analysis showed that LL genotype has a significant protective advantage(OR=0.59,95%CI:0.43~0.82, p<0.01);also found in the L allele carrier group,but no statistically significant(OR=0.90,95%CI:0.62~1.29, p>0.05).LS genotype increases the genetic risk of T2DM(OR=1.46,95%CI:1.07~1.99, p<0.05), S allele carrier group(LS+SS)significant increase the genetic risk of T2DM comparing with the LS genotype group(OR=1.69,95%CI=1.21~2.35, p<0.01).Conclusion The 5-HTTLPR gene polymorphism might be associated with type 2 diabetes mellitus in Shandong Han Population. The S allele significant increases the genetic risk of T2DM.