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 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^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Artikel › Forskning › peer review

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 × 10^-7). In European populations, the rs1387153 T allele is associated with increased FPG (β = 0.06 mmol/l, P = 7.6 × 10 ^-29, N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95% CI = 1.08-1.22, P = 6.3 × 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.

Originalsprog	Engelsk
Sider (fra-til)	89-94
Antal sider	6
Tidsskrift	Nature Genetics
Vol/bind	41
Udgave nummer	1
DOI	https://doi.org/10.1038/ng.277
Status	Udgivet - jan. 2009

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10.1038/ng.277

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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

@article{83d7deb1e67a48be83cfe01b491b9059,

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 × 10-7). In European populations, the rs1387153 T allele is associated with increased FPG (β = 0.06 mmol/l, P = 7.6 × 10 -29, N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95\% CI = 1.08-1.22, P = 6.3 × 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 Ch{\`e}vre, \{Jean Claude\} and Knut Borch-Johnsen and Hartikainen, \{Anna Liisa\} 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 Jarvelin, \{Marjo Riita\} and Walley, \{Andrew J.\} and Torben Hansen and Christian Dina and Oluf Pedersen and Philippe Froguel",

year = "2009",

month = jan,

doi = "10.1038/ng.277",

language = "English",

volume = "41",

pages = "89--94",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

}

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, JC, Borch-Johnsen, K, Hartikainen, AL, 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, MR, 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, bind 41, nr. 1, s. 89-94. https://doi.org/10.1038/ng.277

TY - JOUR

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

PY - 2009/1

Y1 - 2009/1

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 × 10-7). In European populations, the rs1387153 T allele is associated with increased FPG (β = 0.06 mmol/l, P = 7.6 × 10 -29, N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95% CI = 1.08-1.22, P = 6.3 × 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 × 10-7). In European populations, the rs1387153 T allele is associated with increased FPG (β = 0.06 mmol/l, P = 7.6 × 10 -29, N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95% CI = 1.08-1.22, P = 6.3 × 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.

UR - https://www.scopus.com/pages/publications/58149175143

U2 - 10.1038/ng.277

DO - 10.1038/ng.277

M3 - Article

C2 - 19060909

AN - SCOPUS:58149175143

SN - 1061-4036

VL - 41

SP - 89

EP - 94

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

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

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