Endocrine Abstracts

Introduction

The MTNR1B gene encodes a receptor for melatonin, a hormone that controls biorhythms. The gene is expressed primarily in the brain, but also in human pancreatic cells. Genetic studies suggest that variability in the MTNR1B gene is one of the factors sought to influence the pathophysiology of type 2 diabetes mellitus (T2DM). The single nucleotide polymorphism rs10830963 shows the strongest association. Our aim was to compare the distribution of the genetic variant rs10830963 among persons with different glucose tolerance. Subjects with impaired fasting blood glucose (IFG) and impaired glucose tolerance (IGT) during the oral glucose tolerance test (OGTT) were compared with controls. Another goal was to evaluate the possible associations of the polymorphism with insulin sensitivity (IS). Indices of IS, beta cell function and hepatic extraction were calculated and shape of glucose, insulin and C-peptide trajectories during the OGTT (monophasic, biphasic or more complex) were analysed.

Methods

A total of 1206 volunteers were examined biochemically, anthropometrically and underwent a 3 h OGTT (75 g glucose). Genotyping was performed on a TaqMan (LC480, Roche), the NCSS 2004 program was used for statistical evaluation.

Results

13 persons were diagnosed with T2DM, 119 had IFG or IGT and 1074 showed normal results. Higher frequency of minor and in relation to T2DM risk allele G was found in the IFG/IGT group (40.7% vs. 32.4% in controls, P = 0.01), OR = 1.57, CI 95% [1.06; 2.33], P = 0.03). The GG constellation was present in 23% of diabetics, in 17% of the IFG/IGT probands and in 11% of controls (Chi² = 11.2, P = 0.02). GG homozygotes showed slightly higher basal glycemia compared to CC homozygotes (P = 0.01) and also higher stimulated glycemia (AUCgly) in comparison with CC homozygotes (P = 0.002) and with heterozygotes (P = 0.004). GG genotype showed lower OGIS index of IS and lower HOMA-B and IGI indices of beta cell function. No association of the genotype with hepatic extraction or with the shape of glucose, insulin and C-peptide trajectories was observed.

Conclusion

In the sample of the Czech population we confirm the association of the G allele of the rs10830963 polymorphism in the MTNR1B gene with glucose metabolism. The risk allele G is more frequent in people with impaired glycoregulation and homozygous carriers of this allele show higher blood glucose levels during the OGTT and lower indices of IS and beta cell function.

Grant support: AZV CR NU20-01-00308, MH CR RVO EÚ00023761