A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
---|---|
Journal | Nature Genetics |
Volume | 41 |
Issue number | 1 |
Pages (from-to) | 89-94 |
Number of pages | 5 |
ISSN | 1061-4036 |
DOIs | |
Publication status | Published - 2009 |
Bibliographical note
Keywords: Adaptor Proteins, Signal Transducing; Adolescent; Adult; Blood Glucose; Child; Chromosomes, Human, Pair 11; Cohort Studies; Diabetes Mellitus, Type 2; Fasting; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Glucokinase; Humans; Insulin Resistance; Islets of Langerhans; Meta-Analysis as Topic; Middle Aged; Polymorphism, Single Nucleotide; RNA, Messenger; Receptor, Melatonin, MT2; Receptors, Melatonin; Reproducibility of Results
ID: 11550950