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The rs10830963 Polymorphism of the MTNR1B Gene: Association With Abnormal Glucose, Insulin and C-peptide Kinetics

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    0558030 - FGÚ 2023 RIV CH eng J - Článek v odborném periodiku
    Vejražková, D. - Vaňková, M. - Včelák, J. - Krejčí, H. - Anderlová, K. - Tura, A. - Pacini, G. - Sumová, Alena - Sládek, Martin - Bendlová, B.
    The rs10830963 Polymorphism of the MTNR1B Gene: Association With Abnormal Glucose, Insulin and C-peptide Kinetics.
    Frontiers in Endocrinology. Roč. 13, Jun 6 (2022), č. článku 868364. ISSN 1664-2392. E-ISSN 1664-2392
    Institucionální podpora: RVO:67985823
    Klíčová slova: type 2 daibetes mellitus * insulin sensitivity * beta cell function * MTNR1B gene * rs10830963 * OGTT trajectories * glucose tolerance
    Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
    Impakt faktor: 6.055, rok: 2021
    Způsob publikování: Open access
    https://doi.org/10.3389/fendo.2022.868364

    Background: The MTNR1B 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 MTNR1B 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.Results: 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.Conclusion: 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.
    Trvalý link: http://hdl.handle.net/11104/0331843

     
     
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