DOI: 10.18413/2658-6533-2023-9-3-0-3

Analysis of polymorphic variants of serotonin and gamma-aminobutyric acid receptor genes in patients with type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is an expanding global health problem of the 21st century. There has been a global increase in the number of patients with T2DM. It has established a strong association of obesity and age with T2DM. The aim of the study: To analyze polymorphic variants of the serotonin receptor genes HTRD rs674386, HTR1F rs56398417, HTR2A rs6313, HTR3A rs1062613, HTR2C rs6318, the gamma-aminobutyric acid receptor gene GABRA2 rs279845, in patients with type 2 diabetes living in the Republic of Bashkortostan. Materials and methods: DNA samples included a group of patients with T2DM – 691 individuals and control – 1096 individuals. The study of polymorphic markers was carried out using the polymerase chain reaction (PCR) TaqMan. Results: As a result of the study of 6 polymorphic loci of the genes of the neurotransmitter system, protective markers were identified, including the CT and CC genotypes of the rs1062613 polymorphic locus of the HTR3A gene (OR=0.73, Pcor_FDR=0.0007) and the GC and CC risk genotypes of the rs6318 polymorphic locus of the HTR2C gene (OR=2.21, Pcor_FDR =0.0045) among women, the CC genotype is also at risk among men (R=4.05, Pcor_FDR=0.0045). Multilocus analysis of combinations of genotypes and alleles revealed five combinations of increased and decreased risk of developing T2DM. The most significant association was found for the combination of HTR3A rs1062613 allele C + HTR2A rs6313 allele A + HTRD rs674386 allele A + HTR1F rs55639841CC genotype (OR=1.74, Pcor_FDR=0.0004). The analysis of ROC curves showed that the studied loci HTRD rs674386, HTR1F rs56398417, HTR3A rs1062613, GABRA2 rs279845 and variables such as gender, age of the subjects and the level of BMI included in the construction of the risk calculation model can predict the development of T2DM with a sensitivity of 79.0% and a specificity of 75.0%, the area under the AUC curve was 83.40% (95% CI 83.50-87.40). Conclusion: The results obtained may indicate a high level of prognostic significance of polymorphic variants of the genes of the neurotransmitter system in the formation of predisposition to T2DM.

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