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

Nabila Bouatia-Naji; Amélie Bonnefond; Christine Cavalcanti-Proença; Thomas Sparsø; Johan Holmkvist; Marion Marchand; Jérôme Delplanque; Stéphane Lobbens; Ghislain Rocheleau; Emmanuelle Durand; Franck De Graeve; Jean-Claude Chèvre; Knut Borch-Johnsen; Anna-Liisa Hartikainen; Aimo Ruokonen; Jean Tichet; Michel Marre; Jacques Weill; Barbara Heude; Maithé Tauber; Katleen Lemaire; Frans Schuit; Paul Elliott; Torben Jørgensen; Guillaume Charpentier; Samy Hadjadj; Stéphane Cauchi; Martine Vaxillaire; Robert Sladek; Sophie Visvikis-Siest; Beverley Balkau; Claire Lévy-Marchal; François Pattou; David Meyre; Alexandra I F Blakemore; Marjo-Riita Jarvelin; Andrew J Walley; Torben Hansen; Christian Dina; Oluf Pedersen; Philippe Froguel

doi:10.1038/ng.277

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

Nabila Bouatia-Naji, Amélie Bonnefond, Christine Cavalcanti-Proença, Thomas Sparsø, Johan Holmkvist, Marion Marchand, Jérôme Delplanque, Stéphane Lobbens, Ghislain Rocheleau, Emmanuelle Durand, Franck De Graeve, Jean-Claude Chèvre, Knut Borch-Johnsen, Anna-Liisa Hartikainen, Aimo Ruokonen, Jean Tichet, Michel Marre, Jacques Weill, Barbara Heude, Maithé TauberKatleen Lemaire, Frans Schuit, Paul Elliott, Torben Jørgensen, Guillaume Charpentier, Samy Hadjadj, Stéphane Cauchi, Martine Vaxillaire, Robert Sladek, Sophie Visvikis-Siest, Beverley Balkau, Claire Lévy-Marchal, François Pattou, David Meyre, Alexandra I F Blakemore, Marjo-Riita Jarvelin, Andrew J Walley, Torben Hansen, Christian Dina, Oluf Pedersen, Philippe Froguel

438 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	41
Issue number	1
Pages (from-to)	89-94
Number of pages	5
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.277
Publication status	Published - 2009

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Bouatia-Naji, N., Bonnefond, A., Cavalcanti-Proença, C., Sparsø, T., Holmkvist, J., Marchand, M., Delplanque, J., Lobbens, S., Rocheleau, G., Durand, E., De Graeve, F., Chèvre, J-C., Borch-Johnsen, K., Hartikainen, A-L., Ruokonen, A., Tichet, J., Marre, M., Weill, J., Heude, B., ... Froguel, P. (2009). A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nature Genetics, 41(1), 89-94. https://doi.org/10.1038/ng.277

Bouatia-Naji, N, Bonnefond, A, Cavalcanti-Proença, C, Sparsø, T, Holmkvist, J, Marchand, M, Delplanque, J, Lobbens, S, Rocheleau, G, Durand, E, De Graeve, F, Chèvre, J-C, Borch-Johnsen, K, Hartikainen, A-L, Ruokonen, A, Tichet, J, Marre, M, Weill, J, Heude, B, Tauber, M, Lemaire, K, Schuit, F, Elliott, P, Jørgensen, T, Charpentier, G, Hadjadj, S, Cauchi, S, Vaxillaire, M, Sladek, R, Visvikis-Siest, S, Balkau, B, Lévy-Marchal, C, Pattou, F, Meyre, D, Blakemore, AIF, Jarvelin, M-R, Walley, AJ, Hansen, T, Dina, C, Pedersen, O & Froguel, P 2009, 'A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk', Nature Genetics, vol. 41, no. 1, pp. 89-94. https://doi.org/10.1038/ng.277

@article{bbef570019ea11deb43e000ea68e967b,

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

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.",

author = "Nabila Bouatia-Naji and Am{\'e}lie Bonnefond and Christine Cavalcanti-Proen{\c c}a and Thomas Spars{\o} and Johan Holmkvist and Marion Marchand and J{\'e}r{\^o}me Delplanque and St{\'e}phane Lobbens and Ghislain Rocheleau and Emmanuelle Durand and {De Graeve}, Franck and Jean-Claude Ch{\`e}vre and Knut Borch-Johnsen and Anna-Liisa Hartikainen and Aimo Ruokonen and Jean Tichet and Michel Marre and Jacques Weill and Barbara Heude and Maith{\'e} Tauber and Katleen Lemaire and Frans Schuit and Paul Elliott and Torben J{\o}rgensen and Guillaume Charpentier and Samy Hadjadj and St{\'e}phane Cauchi and Martine Vaxillaire and Robert Sladek and Sophie Visvikis-Siest and Beverley Balkau and Claire L{\'e}vy-Marchal and Fran{\c c}ois Pattou and David Meyre and Blakemore, {Alexandra I F} and Marjo-Riita Jarvelin and Walley, {Andrew J} and Torben Hansen and Christian Dina and Oluf Pedersen and Philippe Froguel",

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",

year = "2009",

doi = "10.1038/ng.277",

language = "English",

volume = "41",

pages = "89--94",

journal = "Nature: New biology",

issn = "1061-4036",

publisher = "nature publishing group",

number = "1",

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T1 - A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk

AU - Bouatia-Naji, Nabila

AU - Bonnefond, Amélie

AU - Cavalcanti-Proença, Christine

AU - Sparsø, Thomas

AU - Holmkvist, Johan

AU - Marchand, Marion

AU - Delplanque, Jérôme

AU - Lobbens, Stéphane

AU - Rocheleau, Ghislain

AU - Durand, Emmanuelle

AU - De Graeve, Franck

AU - Chèvre, Jean-Claude

AU - Borch-Johnsen, Knut

AU - Hartikainen, Anna-Liisa

AU - Ruokonen, Aimo

AU - Tichet, Jean

AU - Marre, Michel

AU - Weill, Jacques

AU - Heude, Barbara

AU - Tauber, Maithé

AU - Lemaire, Katleen

AU - Schuit, Frans

AU - Elliott, Paul

AU - Jørgensen, Torben

AU - Charpentier, Guillaume

AU - Hadjadj, Samy

AU - Cauchi, Stéphane

AU - Vaxillaire, Martine

AU - Sladek, Robert

AU - Visvikis-Siest, Sophie

AU - Balkau, Beverley

AU - Lévy-Marchal, Claire

AU - Pattou, François

AU - Meyre, David

AU - Blakemore, Alexandra I F

AU - Jarvelin, Marjo-Riita

AU - Walley, Andrew J

AU - Hansen, Torben

AU - Dina, Christian

AU - Pedersen, Oluf

AU - Froguel, Philippe

N1 - 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

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1038/ng.277

DO - 10.1038/ng.277

M3 - Journal article

C2 - 19060909

SN - 1061-4036

VL - 41

SP - 89

EP - 94

JO - Nature: New biology

JF - Nature: New biology

IS - 1

ER -

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

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