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The rs10830963 Polymorphism of the MTNR1B Gene: Association With Abnormal Glucose, Insulin and C-peptide Kinetics
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SYSNO ASEP 0558030 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The rs10830963 Polymorphism of the MTNR1B Gene: Association With Abnormal Glucose, Insulin and C-peptide Kinetics Author(s) Vejražková, D. (CZ)
Vaňková, M. (CZ)
Včelák, J. (CZ)
Krejčí, H. (CZ)
Anderlová, K. (CZ)
Tura, A. (IT)
Pacini, G. (IT)
Sumová, Alena (FGU-C) RID, ORCID
Sládek, Martin (FGU-C) RID, ORCID, SAI
Bendlová, B. (CZ)Article number 868364 Source Title Frontiers in Endocrinology. - : Frontiers Media - ISSN 1664-2392
Roč. 13, Jun 6 (2022)Number of pages 9 s. Language eng - English Country CH - Switzerland Keywords type 2 daibetes mellitus ; insulin sensitivity ; beta cell function ; MTNR1B gene ; rs10830963 ; OGTT trajectories ; glucose tolerance OECD category Endocrinology and metabolism (including diabetes, hormones) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000813181100001 EID SCOPUS 85133381372 DOI 10.3389/fendo.2022.868364 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://doi.org/10.3389/fendo.2022.868364
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