Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czechia.
Department of Obstetrics and Gynecology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.
Front Endocrinol (Lausanne). 2022 Jun 6;13:868364. doi: 10.3389/fendo.2022.868364. eCollection 2022.
The gene encodes a receptor for melatonin, a hormone regulating biorhythms. Disruptions in biorhythms contribute to the development of type 2 diabetes mellitus (T2DM). Genetic studies suggest that variability in the gene affects T2DM development. Our aim was to compare the distribution of the genetic variant rs10830963 between persons differing in glucose tolerance in a sample of the Czech population (N=1206). We also evaluated possible associations of the polymorphism with insulin sensitivity, beta cell function, with the shape of glucose, insulin and C-peptide trajectories measured 7 times during a 3-hour oral glucose tolerance test (OGTT) and with glucagon response. In a subgroup of 268 volunteers we also evaluated sleep patterns and biorhythm.
13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) and/or impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFG/IGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFG/IGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFG/IGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women.
In a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.
该基因编码褪黑素受体，褪黑素是一种调节生物节律的激素。生物节律紊乱会导致 2 型糖尿病（T2DM）的发生。遗传研究表明， 基因的变异会影响 T2DM 的发生。我们的目的是比较 rs10830963 基因在捷克人群样本中葡萄糖耐量不同的个体之间的分布情况（N=1206）。我们还评估了该多态性与胰岛素敏感性、β细胞功能、在口服葡萄糖耐量试验（OGTT）期间测量的 7 次葡萄糖、胰岛素和 C 肽轨迹的形状以及胰高血糖素反应之间的可能关联。在 268 名志愿者的亚组中，我们还评估了睡眠模式和生物节律。
13 人被诊断为 T2DM，119 人存在空腹血糖受损（IFG）和/或糖耐量受损（IGT）。1074 名参与者结果正常，形成对照组。与对照组相比，IFG/IGT 组中 G 等位基因的频率较高。糖尿病患者中 GG 基因型的存在率为 23%，IFG/IGT 患者为 17%，对照组为 11%。与 CC 和 CG 基因型相比，GG 纯合子在 OGTT 中表现出更高的刺激血糖水平。携带 G 等位基因的纯合子和杂合子均表现出胰岛素和 C 肽分泌的早期阶段较低，而胰岛素敏感性不变。排除糖尿病和 IFG/IGT 组后，这些差异仍然显著。未观察到基因型与 OGTT 基于轨迹、胰高血糖素或生物钟模式的形状之间存在关联。然而，OGTT 轨迹的形状在男性和女性之间存在显著差异。
在捷克人群的代表性样本中，rs10830963 多态性的 G 等位基因与早期β细胞功能受损相关，即使在健康个体中也是如此。
