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

被引：455

作者：

Bouatia-Naji, Nabila ^{[1
,2
]}

Bonnefond, Amelie ^{[1
,2
]}

Cavalcanti-Proenca, Christine ^{[1
,2
]}

Sparso, Thomas ^{[3
]}

Holmkvist, Johan ^{[3
]}

Marchand, Marion ^{[1
,2
]}

Delplanque, Jerome ^{[1
,2
]}

Lobbens, Stephane ^{[1
,2
]}

Rocheleau, Ghislain ^{[4
,5
,6
]}

Durand, Emmanuelle ^{[1
,2
]}

De Graeve, Franck ^{[1
,2
]}

Chevre, Jean-Claude ^{[1
,2
]}

Borch-Johnsen, Knut ^{[3
,7
]}

Hartikainen, Anna-Liisa ^{[8
]}

Ruokonen, Aimo ^{[9
]}

Tichet, Jean ^{[10
]}

Marre, Michel ^{[11
,12
]}

Weill, Jacques ^{[13
]}

Heude, Barbara ^{[14
,15
]}

Tauber, Maithe ^{[16
]}

Lemaire, Katleen ^{[17
]}

Schuit, Frans ^{[17
]}

Elliott, Paul ^{[18
]}

Jorgensen, Torben ^{[19
,20
]}

Charpentier, Guillaume ^{[21
]}

Hadjadj, Samy ^{[22
]}

Cauchi, Stephane ^{[1
,2
]}

Vaxillaire, Martine ^{[1
,2
]}

Sladek, Robert ^{[4
,5
]}

Visvikis-Siest, Sophie ^{[23
]}

Balkau, Beverley ^{[14
,15
]}

Levy-Marchal, Claire ^{[24
,25
]}

Pattou, Francois ^{[26
]}

Meyre, David ^{[1
,2
]}

Blakemore, Alexandra I. F. ^{[27
]}

Jarvelin, Marjo-Riita ^{[18
,28
,29
]}

Walley, Andrew J. ^{[27
]}

Hansen, Torben ^{[3
,30
]}

Dina, Christian ^{[1
,2
]}

Pedersen, Oluf ^{[3
,7
,20
]}

Froguel, Philippe ^{[1
,2
,27
]}

机构：

[1] CNRS, Inst Biol, UMR 8090, F-59019 Lille, France

[2] Univ Lille 2, Inst Pasteur, F-59019 Lille, France

[3] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[4] McGill Univ, Fac Med, Dept Human Genet, Montreal, PQ H3H 1P3, Canada

[5] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada

[6] Prognomix, Montreal, PQ H1Y 3L1, Canada

[7] Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus C, Denmark

[8] Univ Oulu, Dept Clin Sci Obstet & Gynecol, FIN-90014 Oulu, Finland

[9] Univ Oulu, Dept Clin Sci Clin Chem, FIN-90014 Oulu, Finland

[10] Inst Inter Reg Sante IRSA, F-37521 La Riche, France

[11] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, F-75018 Paris, France

[12] Univ Paris 07, INSERM, U695, F-75870 Paris, France

[13] Jeanne Flandre Hosp, Pediatr Endocrine Unit, F-59800 Lille, France

[14] INSERM, U780, F-94807 Villejuif, France

[15] Univ Paris Sud, F-91405 Orsay, France

[16] Childrens Hosp, CHU, INSERM, U563, F-31059 Toulouse, France

[17] Katholieke Univ Leuven, Dept Mol Cell Biol, Gene Express Unit, B-3000 Louvain, Belgium

[18] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England

[19] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark

[20] Univ Copenhagen, Fac Hlth Sci, DK-2200 Copenhagen, Denmark

[21] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, F-91108 Essonnes, France

[22] Univ Poitiers, INSERM, UFR Med Pharm, Ctr Hosp Univ Poitiers,U927,CIC 0802, F-86034 Poitiers, France

[23] INSERM, Cardiovasc Genet team, CIC 9501, F-54000 Nancy, France

[24] Hop Robert Debre, INSERM, U690, F-75019 Paris, France

[25] Paris Diderot Univ, F-75005 Paris, France

[26] Univ Lille Nord France, CHRU Lille, INSERM, U859, F-59045 Lille, France

[27] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England

[28] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[29] Univ Oulu, Bioctr Oulu, FIN-90014 Oulu, Finland

[30] Univ So Denmark, Fac Hlth Sci, DK-5230 Odense, Denmark

来源：

NATURE GENETICS | 2009年 / 41卷 / 01期

基金：

英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; INSULIN-RESISTANCE; GENE; MELATONIN; POLYMORPHISM; COHORT;

D O I：

10.1038/ng.277

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：89 / 94

页数：6

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