Genetic variants of the glucagon-like receptor-1 in obesity

A. Nikulina
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Abstract

Introduction and aim. Dysfunction of the glucagon-like peptide 1 (GLP-1)/GLP-1 receptor (GLP-1R) axis promotes obesity and metabolic disorders. The aim was to study the associations of the single nucleotide variants (SNV) GLP1R gene with proinflammatory cytokines and metabolic disorders in children with various obesity phenotypes. Material and methods. 252 children with obesity aged 6-18 years were examined. The first group (n=152) was represented by children with metabolically unhealthy obesity (MUO). The second group (n=100) consolidated of children with metabolically healthy obesity (MHO). Whole genome sequencing (CeGat, Germany) was performed in 52 children. Results. An association with the development of obesity was noted for T alleles rs61754624 (t=3.33) and rs10305457 (t=2.06); with MUO – for C alleles rs1042044 (t=2.23), rs1126476 (t=2.63), rs2235868 (t=2.82); T alleles rs61754624 (t=3.33), rs10305457 (t=2.06) GLP1R, p<0.05. In the MHO group, a correlation was found with the levels of pro-inflammatory markers IL-1β, IL-6 in the presence of the GA genotype SNV rs3765468; with hyperglycemia - GA genotype SNV rs6923761, CC genotype SNV rs1042044, AA rs6918287; hyperinsulinemia - GA genotype SNV rs3765468, GG rs10305421; triglyceridemia - AA rs6918287 of GLP1R. Conclusion. SNV rs1042044, rs3765468, rs6923761, s6918287, and rs rs10305421 GLP1R are associated with the development of MUO in individuals with MHO.
肥胖症中胰高血糖素样受体-1的遗传变异
引言和目的。胰高血糖素样肽 1(GLP-1)/GLP-1 受体(GLP-1R)轴的功能障碍会促进肥胖和代谢紊乱。目的是研究单核苷酸变异(SNV)GLP1R 基因与各种肥胖表型儿童的促炎细胞因子和代谢紊乱的关系。材料和方法研究对象为 252 名 6-18 岁肥胖症儿童。第一组(人数=152)为代谢性不健康肥胖(MUO)儿童。第二组(人数=100)为代谢健康型肥胖(MHO)儿童。对 52 名儿童进行了全基因组测序(德国 CeGat 公司)。结果显示T等位基因rs61754624(t=3.33)和rs10305457(t=2.06)与肥胖的发生有关;MUO等位基因rs61754624(t=3.33)和rs10305457(t=2.06)与肥胖的发生有关。06);MUO--C等位基因rs1042044(t=2.23)、rs1126476(t=2.63)、rs2235868(t=2.82);T等位基因rs61754624(t=3.33)、rs10305457(t=2.06)GLP1R,p<0.05。在 MHO 组中,GLP1R 的 GA 基因型 SNV rs3765468 与促炎症标志物 IL-1β、IL-6 水平相关;GA 基因型 SNV rs6923761、CC 基因型 SNV rs1042044、AA rs6918287 与高血糖相关;GLP1R 的 GA 基因型 SNV rs3765468、GG rs10305421 与高胰岛素血症相关;GLP1R 的 AA rs6918287 与甘油三酯血症相关。结论GLP1R 的 SNV rs1042044、rs3765468、rs6923761、s6918287 和 rs rs10305421 与 MHO 患者 MUO 的发生有关。
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