A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk
Open accessAbstract
In genome-wide association (GWA) data from 2,151 nondiabetic French subjects, we identified rs1387153, near MTNR1B (which encodes the melatonin receptor 2 (MT2)), as a modulator of fasting plasma glucose (FPG; P = 1.3 x 10(-7)). In European populations, the rs1387153 T allele is associated with increased FPG (beta = 0.06 mmol/l, P = 7.6 x 10(-29), N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95% CI = 1.08-1.22, P = 6.3 x 10(-5), cases N = 6,332) and risk of developing hyperglycemia or diabetes over a 9-year period (hazard ratio (HR) = 1.20, 95% CI = 1.06-1.36, P = 0.005, incident cases N = 515). RT-PCR analyses confirm the presence of MT2 transcripts in neural tissues and show MT2 expression in human pancreatic islets and beta cells. Our data suggest a possible link between circadian rhythm regulation and glucose homeostasis through the melatonin signaling pathway.
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Although associations of cortisol and melatonin concentrations to insulin action have been reported in the literature, the authors did not find such a link in the present study.
“Therefore, although associations of cortisol and melatonin concentrations to insulin action have been reported in the literature (29,30), we did not find such a link in the present study.”
From Diurnal Pattern of Insulin Action in Type 1 Diabetes (2013) · cites this paper as [29]
Individuals with certain genotypes, such as polymorphisms in the melatonin receptor 1B (MTNR1B) gene, may require monitoring of hemoglobin A1C if they take supplemental melatonin.
“Those with certain genotypes, such as polymorphisms in the melatonin receptor 1B (MTNR1B) gene, may require monitoring of hemoglobin A1C if they take supplemental melatonin [275,276].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [276]
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- Authors
- Bouatia-Naji, N., Bonnefond, A., Cavalcanti-Proença, C., Sparsø, T., Holmkvist, J., Marchand, M., Delplanque, J., Lobbens, S., Rocheleau, G., Durand, E., De Graeve, F., Chèvre, J.-C., Borch-Johnsen, K., Hartikainen, A.-L., Ruokonen, A., Tichet, J., Marre, M., Weill, J., Heude, B., Tauber, M., Lemaire, K., Schuit, F., Elliott, P., Jørgensen, T., Charpentier, G., Hadjadj, S., Cauchi, S., Vaxillaire, M., Sladek, R., Visvikis-Siest, S., Balkau, B., Lévy-Marchal, C., Pattou, F., Meyre, D., Blakemore, A. I. F., Jarvelin, M.-R., Walley, A. J., Hansen, T., Dina, C., Pedersen, O., & Froguel, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- McGill University and Génome Québec Innovation Centre (CA)
- University of Oulu (FI)
- Inserm (FR)
- Hôpital Jeanne de Flandre (FR)
- Université Paris-Sud (FR)
- KU Leuven (BE)
- Imperial College London (GB)
- University of Copenhagen (DK)
- Centre Hospitalier Sud Francilien (FR)
- Hammersmith Hospital (GB)
- University of Southern Denmark (DK)
- Corresponding author
- Froguel, Philippe
- ORCID
- Bonnefond, Amélie
- Rocheleau, Ghislain
- Durand, Emmanuelle
- Chèvre, Jean-Claude
- Marre, Michel
- Heude, Barbara
- Tauber, Maithé
- Lemaire, Katleen
- Schuit, Frans
- Elliott, Paul
- Jørgensen, Torben
- Charpentier, Guillaume
- Hadjadj, Samy
- Cauchi, Stéphane
- Vaxillaire, Martine
- Sladek, Robert
- Balkau, Beverley
- Pattou, François
- Meyre, David
- Blakemore, Alexandra I F
- Walley, Andrew J
- Hansen, Torben
- Pedersen, Oluf
- Froguel, Philippe
- Venue
- Nature Genetics
- Published
- 2008-12-07
- Volume
- 41
- Issue
- 1
- Pages
- 89-94
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2153171441
- Cited by
- 611
- References
- 31
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 23 · 2023: 25 · 2022: 15 · 2021: 27 · 2020: 21 · 2019: 28 · 2018: 27 · 2017: 36 · 2016: 36 · 2015: 41 · 2014: 45 · 2013: 30 · 2012: 48
- FWCI
- 27.98
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Lirias (submittedVersion, other-oa)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Eli Lilly and Company
- Sanofi
- Sundhed og Sygdom, Det Frie Forskningsråd
- Ministeriet for Fø devarer, Landbrug og Fiskeri
- Genome Canada
- Les Laboratories Pierre Fabre
- European Commission (LSHM-CT-2006-518153, LSHM-CT-2004-512013, QLG1‐CT‐2000‐01643)
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Lundbeckfonden
- Novo Nordisk
- Vetenskapsrådet
- Fondation de France
- Oulun Yliopisto
- Servier
- H. Lundbeck A/S
- Diabetesforeningen
- Novartis Pharma
- Medical Research Council
- Biocenter, University of Oulu
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- MTNR1B, melatonin receptor 2, type 2 diabetes, fasting blood glucose, genetic association, circadian rhythm, glucose homeostasis, melatonin signaling, pancreatic beta cells
- MeSH terms
- Adolescent, Adult, Blood Glucose, Child, Chromosomes, Human, Pair 11, Diabetes Mellitus, Type 2, Fasting, Gene Expression Regulation, Glucokinase, Humans, Insulin Resistance, Islets of Langerhans, Middle Aged, RNA, Messenger, Meta-Analysis as Topic, Reproducibility of Results, Cohort Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Gene Expression Profiling, Receptors, Melatonin, Receptor, Melatonin, MT2, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study
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