SLC6A45HTTLPR Polymorphism Affects Insulin Secretion in Patients with Polycystic Ovary Syndrome

Abstract

Purpose To investigate in a pilot study of genetic polymorphisms in serotonin system influencing basal- and glucose-stimulated insulin secretion in women with polycystic ovary syndrome (PCOS). Methods A cross-sectional study included 65 female patients with PCOS followed up at the endocrine outpatient clinic of the University Medical Center Ljubljana and a control group of 94 young healthy female blood donors. Oral glucose tolerance test was performed only in PCOS patients and basal- and glucose-stimulated blood glucose and insulin levels were measured. All the subjects were genotyped for 5HTR1A rs6295, 5HTR1B rs13212041, and SLC6A4 5HTTLPR polymorphisms in the serotonin system. Results Genotype distributions were in accordance with the Hardy-Weinberg equilibrium (HWE), except for 5HTR1A rs6295 in healthy controls and 5HTR1B rs13212041 in PCOS patients that were not consistent with HWE. SLC6A4 5HTTLPR polymorphism was significantly associated with insulin secretion (p = 0.030) and with the area under the curve of insulin blood levels during OGTT (p = 0.021). None of the investigated polymorphisms was significantly associated with basal- or glucose-stimulated blood glucose levels at any point in time during OGTT or with the basal insulin concentration. Conclusions Serotonin system may play a role in glucose-stimulated insulin secretion in patients with insulin resistance (IR) and decreased insulin sensitivity. Further studies are needed to conclude whether the observed effect is characteristic for PCOS-related metabolic disturbances or for the identified mutation in different high metabolic risk populations.

Identification and Validation of Autophagy-Related Genes in Primary Ovarian Insufficiency by Gene Expression Profile and Bioinformatic Analysis

“…SLC6A4 encodes an integral membrane protein, which act as the role to transport the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. SLC6A4 5HTTLPR polymorphism was revealed to be related to insulin blood levels and insulin secretion during OGTT in patients with polycystic ovary syndrome (PCOS) [ 39 ]. Recent research has implied that BSN acted in concert to control presynaptic autophagy [ 40 ].…”

The Potential Effect of Rhizoma coptidis on Polycystic Ovary Syndrome Based on Network Pharmacology and Molecular Docking

“…Decreased Drd2 expression in the Evidence-Based Complementary and Alternative Medicine theca was related to an increased vascularization in the theca of PCOS follicles, and overproduction of VEGF may lead to ovarian hyperstimulation syndrome [36,38]. SLC6A4 5HTTLPR polymorphism was related to insulin secretion and insulin blood levels during OGTT in patients with PCOS [39]. CDK2 is a cell cycle regulator, and the PCOS condition is related to the increased nuclear abundance of CDK2 in the endometrial epithelial cells [40].…”

Association of the Effect of SLC6A4 Gene Polymorphisms on the Risk of Diabetes‏

“…A study showed the role of the SLC6A4 gene in insulin secretion in patients with polycystic ovary syndrome. Polymorphism in SERT alters insulin secretion in these individuals (27). The discovery of these genetic changes in diabetes reveals the functional role of genetic changes in the development of the disease.…”