Variants in MTNR1B influence fasting glucose levels

Nat Genet. 2009 Jan;41(1):77-81. doi: 10.1038/ng.290. Epub 2008 Dec 7.

Abstract

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / genetics*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology
  • Fasting / blood*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Meta-Analysis as Topic
  • Polymorphism, Single Nucleotide / genetics*
  • Quantitative Trait Loci / genetics
  • Receptor, Melatonin, MT2 / genetics*
  • Receptors, Melatonin / genetics*

Substances

  • Blood Glucose
  • Receptor, Melatonin, MT2
  • Receptors, Melatonin

Grant support