title: Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans.
abstract: OBJECTIVE
  The common MTNR1B genetic variant rs10830963 is associated with an increased risk of type 2 diabetes (T2D). To date, no experimental study has tested the effect of the MTNR1B variant on glucose metabolism in humans during exposure of the melatonin receptors to their ligand. The aim of this study was to investigate whether this MTNR1B variant influenced the effect of melatonin (5mg) on glucose tolerance assessed by an oral glucose tolerance test (OGTT; 75 g) at different times of the day (morning and evening) as compared to a placebo.
  
  
  METHODS
  Seventeen normoglycemic women (24 ± 6 years; BMI 23.0 ± 3.3 kg/m(2)) completed the study (11 carriers of the risk allele [CG] and 6 noncarriers [CC]).
  
  
  RESULTS
  The effect of melatonin on glucose tolerance depended on the genotype. In the morning, the effect of melatonin (melatonin-placebo) on the glucose area under the curve (AUC) above baseline differed significantly (P=0.036) between the carriers and noncarriers. This effect of melatonin in the carriers was six times as large as that in the noncarriers. The MTNR1B SNP explained over one-quarter (26%) of the inter-individual differences in the effect of melatonin on glucose AUC. However, in the evening, the effect of melatonin on glucose AUC of the carriers and noncarriers did not differ significantly (P>0.05).
  
  
  CONCLUSIONS
  MTNR1B rs10830963 risk variant worsens the effect of melatonin on glucose tolerance, suggesting the importance of genotyping and personalized recommendations, especially in people consuming food when melatonin levels are elevated. Large-scale studies in vulnerable populations are necessary to translate these results into real-world, clinically relevant recommendations.
authors.affiliation: Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain; IMIB-Arrixaca, Murcia, Spain. Electronic address: garaulet@um.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Garaulet
authors.affiliation: Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain; IMIB-Arrixaca, Murcia, Spain. Electronic address: puriki4@hotmail.com.
authors.forename: Purificación
authors.initials: P
authors.lastname: Gómez-Abellán
authors.affiliation: Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain; IMIB-Arrixaca, Murcia, Spain. Electronic address: patrirru@hotmail.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rubio-Sastre
authors.affiliation: Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain; IMIB-Arrixaca, Murcia, Spain. Electronic address: jamadrid@um.es.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Madrid
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA. Electronic address: fscheer@bwh.harvard.edu.
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C573871:MTNR1B protein, human; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
keywords: Genetic variation; Glucose tolerance; MTNR1B; Melatonin; Type 2 diabetes