A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk.
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.
Bouatia-Naji
Nabila
N
CNRS-UMR-8090, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.
Bonnefond
Amélie
A
Cavalcanti-Proença
Christine
C
Sparsø
Thomas
T
Holmkvist
Johan
J
Marchand
Marion
M
Delplanque
Jérôme
J
Lobbens
Stéphane
S
Rocheleau
Ghislain
G
Durand
Emmanuelle
E
De Graeve
Franck
F
Chèvre
Jean-Claude
JC
Borch-Johnsen
Knut
K
Hartikainen
Anna-Liisa
AL
Ruokonen
Aimo
A
Tichet
Jean
J
Marre
Michel
M
Weill
Jacques
J
Heude
Barbara
B
Tauber
Maithé
M
Lemaire
Katleen
K
Schuit
Frans
F
Elliott
Paul
P
Jørgensen
Torben
T
Charpentier
Guillaume
G
Hadjadj
Samy
S
Cauchi
Stéphane
S
Vaxillaire
Martine
M
Sladek
Robert
R
Visvikis-Siest
Sophie
S
Balkau
Beverley
B
Lévy-Marchal
Claire
C
Pattou
François
F
Meyre
David
D
Blakemore
Alexandra I F
AI
Jarvelin
Marjo-Riita
MR
Walley
Andrew J
AJ
Hansen
Torben
T
Dina
Christian
C
Pedersen
Oluf
O
Froguel
Philippe
P
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D005215:Fasting / Q000097:blood*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005941:Glucokinase / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000235:genetics* / Q000378:metabolism; D044094:Receptors, Melatonin / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D012333:RNA, Messenger; D044123:Receptor, Melatonin, MT2; D044094:Receptors, Melatonin; D005941:Glucokinase