A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk

Nat Genet. 2009 Jan;41(1):89-94. doi: 10.1038/ng.277. Epub 2008 Dec 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adolescent
  • Adult
  • Blood Glucose / genetics*
  • Child
  • Chromosomes, Human, Pair 11 / genetics
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics*
  • Fasting / blood*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Glucokinase / genetics
  • Humans
  • Insulin Resistance / genetics
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Meta-Analysis as Topic
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Melatonin, MT2 / genetics*
  • Receptor, Melatonin, MT2 / metabolism
  • Receptors, Melatonin / genetics*
  • Receptors, Melatonin / metabolism
  • Reproducibility of Results

Substances

  • Adaptor Proteins, Signal Transducing
  • Blood Glucose
  • GCKR protein, human
  • RNA, Messenger
  • Receptor, Melatonin, MT2
  • Receptors, Melatonin
  • Glucokinase