MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. / Andersson, Ehm A; Holst, Birgitte; Sparsø, Thomas; Grarup, Niels; Banasik, Karina; Holmkvist, Johan; Jørgensen, Torben; Borch-Johnsen, Knut; Egerod, Kristoffer L; Lauritzen, Torsten; Sørensen, Thorkild I A; Bonnefond, Amélie; Meyre, David; Froguel, Philippe; Schwartz, Thue W; Pedersen, Oluf; Hansen, Torben.

In: Diabetes, Vol. 59, No. 6, 2010, p. 1539-48.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Andersson, EA, Holst, B, Sparsø, T, Grarup, N, Banasik, K, Holmkvist, J, Jørgensen, T, Borch-Johnsen, K, Egerod, KL, Lauritzen, T, Sørensen, TIA, Bonnefond, A, Meyre, D, Froguel, P, Schwartz, TW, Pedersen, O & Hansen, T 2010, 'MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans', Diabetes, vol. 59, no. 6, pp. 1539-48. https://doi.org/10.2337/db09-1757

APA

Andersson, E. A., Holst, B., Sparsø, T., Grarup, N., Banasik, K., Holmkvist, J., Jørgensen, T., Borch-Johnsen, K., Egerod, K. L., Lauritzen, T., Sørensen, T. I. A., Bonnefond, A., Meyre, D., Froguel, P., Schwartz, T. W., Pedersen, O., & Hansen, T. (2010). MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. Diabetes, 59(6), 1539-48. https://doi.org/10.2337/db09-1757

Vancouver

Andersson EA, Holst B, Sparsø T, Grarup N, Banasik K, Holmkvist J et al. MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. Diabetes. 2010;59(6):1539-48. https://doi.org/10.2337/db09-1757

Author

Andersson, Ehm A ; Holst, Birgitte ; Sparsø, Thomas ; Grarup, Niels ; Banasik, Karina ; Holmkvist, Johan ; Jørgensen, Torben ; Borch-Johnsen, Knut ; Egerod, Kristoffer L ; Lauritzen, Torsten ; Sørensen, Thorkild I A ; Bonnefond, Amélie ; Meyre, David ; Froguel, Philippe ; Schwartz, Thue W ; Pedersen, Oluf ; Hansen, Torben. / MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. In: Diabetes. 2010 ; Vol. 59, No. 6. pp. 1539-48.

Bibtex

@article{cf668260943a11df928f000ea68e967b,
title = "MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans",
abstract = "OBJECTIVE: Common variants in the melatonin receptor type 1B (MTNR1B) locus have been shown to increase fasting plasma glucose (FPG) and the risk of type 2 diabetes. The aims of this study were to evaluate whether nonsynonymous variants in MTNR1B associate with monogenic forms of hyperglycemia, type 2 diabetes, or related metabolic traits. RESEARCH DESIGN AND METHODS: MTNR1B was sequenced in 47 probands with clinical maturity-onset diabetes of the young (MODY), in 51 probands with early-onset familial type 2 diabetes, and in 94 control individuals. Six nonsynonymous variants (G24E, L60R, V124I, R138C, R231H, and K243R) were genotyped in up to 22,142 Europeans. Constitutive and melatonin-induced signaling was characterized for the wild-type melatonin receptor type 1B (MT2) and the 24E, 60R, and 124I MT2 mutants in transfected COS-7 cells. RESULTS: No mutations in MTNR1B were MODY specific, and none of the investigated MTNR1B variants associated with type 2 diabetes. The common 24E variant associated with increased prevalence of obesity (odds ratio 1.20 [1.08-1.34]; P = 8.3 x 10(-4)) and increased BMI (beta = 0.5 kg/m(2); P = 1.2 x 10(-5)) and waist circumference (beta = 1.2 cm; P = 9 x 10(-6)) in combined Danish and French study samples. 24E also associated with decreased FPG (beta = -0.08 mmol/l; P = 9.2 x 10(-4)) in the Danish Inter99 population. Slightly decreased constitutive activity was observed for the MT2 24E mutant, while the 124I and 60R mutants displayed considerably decreased or completely disrupted signaling, respectively. CONCLUSIONS: Nonsynonymous mutations in MTNR1B are not a common cause of MODY or type 2 diabetes among Danes. MTNR1B 24E associates with increased body mass and decreased FPG. Decreased MT2 signaling does apparently not directly associate with FPG or type 2 diabetes.",
author = "Andersson, {Ehm A} and Birgitte Holst and Thomas Spars{\o} and Niels Grarup and Karina Banasik and Johan Holmkvist and Torben J{\o}rgensen and Knut Borch-Johnsen and Egerod, {Kristoffer L} and Torsten Lauritzen and S{\o}rensen, {Thorkild I A} and Am{\'e}lie Bonnefond and David Meyre and Philippe Froguel and Schwartz, {Thue W} and Oluf Pedersen and Torben Hansen",
year = "2010",
doi = "10.2337/db09-1757",
language = "English",
volume = "59",
pages = "1539--48",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "6",

}

RIS

TY - JOUR

T1 - MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans

AU - Andersson, Ehm A

AU - Holst, Birgitte

AU - Sparsø, Thomas

AU - Grarup, Niels

AU - Banasik, Karina

AU - Holmkvist, Johan

AU - Jørgensen, Torben

AU - Borch-Johnsen, Knut

AU - Egerod, Kristoffer L

AU - Lauritzen, Torsten

AU - Sørensen, Thorkild I A

AU - Bonnefond, Amélie

AU - Meyre, David

AU - Froguel, Philippe

AU - Schwartz, Thue W

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2010

Y1 - 2010

N2 - OBJECTIVE: Common variants in the melatonin receptor type 1B (MTNR1B) locus have been shown to increase fasting plasma glucose (FPG) and the risk of type 2 diabetes. The aims of this study were to evaluate whether nonsynonymous variants in MTNR1B associate with monogenic forms of hyperglycemia, type 2 diabetes, or related metabolic traits. RESEARCH DESIGN AND METHODS: MTNR1B was sequenced in 47 probands with clinical maturity-onset diabetes of the young (MODY), in 51 probands with early-onset familial type 2 diabetes, and in 94 control individuals. Six nonsynonymous variants (G24E, L60R, V124I, R138C, R231H, and K243R) were genotyped in up to 22,142 Europeans. Constitutive and melatonin-induced signaling was characterized for the wild-type melatonin receptor type 1B (MT2) and the 24E, 60R, and 124I MT2 mutants in transfected COS-7 cells. RESULTS: No mutations in MTNR1B were MODY specific, and none of the investigated MTNR1B variants associated with type 2 diabetes. The common 24E variant associated with increased prevalence of obesity (odds ratio 1.20 [1.08-1.34]; P = 8.3 x 10(-4)) and increased BMI (beta = 0.5 kg/m(2); P = 1.2 x 10(-5)) and waist circumference (beta = 1.2 cm; P = 9 x 10(-6)) in combined Danish and French study samples. 24E also associated with decreased FPG (beta = -0.08 mmol/l; P = 9.2 x 10(-4)) in the Danish Inter99 population. Slightly decreased constitutive activity was observed for the MT2 24E mutant, while the 124I and 60R mutants displayed considerably decreased or completely disrupted signaling, respectively. CONCLUSIONS: Nonsynonymous mutations in MTNR1B are not a common cause of MODY or type 2 diabetes among Danes. MTNR1B 24E associates with increased body mass and decreased FPG. Decreased MT2 signaling does apparently not directly associate with FPG or type 2 diabetes.

AB - OBJECTIVE: Common variants in the melatonin receptor type 1B (MTNR1B) locus have been shown to increase fasting plasma glucose (FPG) and the risk of type 2 diabetes. The aims of this study were to evaluate whether nonsynonymous variants in MTNR1B associate with monogenic forms of hyperglycemia, type 2 diabetes, or related metabolic traits. RESEARCH DESIGN AND METHODS: MTNR1B was sequenced in 47 probands with clinical maturity-onset diabetes of the young (MODY), in 51 probands with early-onset familial type 2 diabetes, and in 94 control individuals. Six nonsynonymous variants (G24E, L60R, V124I, R138C, R231H, and K243R) were genotyped in up to 22,142 Europeans. Constitutive and melatonin-induced signaling was characterized for the wild-type melatonin receptor type 1B (MT2) and the 24E, 60R, and 124I MT2 mutants in transfected COS-7 cells. RESULTS: No mutations in MTNR1B were MODY specific, and none of the investigated MTNR1B variants associated with type 2 diabetes. The common 24E variant associated with increased prevalence of obesity (odds ratio 1.20 [1.08-1.34]; P = 8.3 x 10(-4)) and increased BMI (beta = 0.5 kg/m(2); P = 1.2 x 10(-5)) and waist circumference (beta = 1.2 cm; P = 9 x 10(-6)) in combined Danish and French study samples. 24E also associated with decreased FPG (beta = -0.08 mmol/l; P = 9.2 x 10(-4)) in the Danish Inter99 population. Slightly decreased constitutive activity was observed for the MT2 24E mutant, while the 124I and 60R mutants displayed considerably decreased or completely disrupted signaling, respectively. CONCLUSIONS: Nonsynonymous mutations in MTNR1B are not a common cause of MODY or type 2 diabetes among Danes. MTNR1B 24E associates with increased body mass and decreased FPG. Decreased MT2 signaling does apparently not directly associate with FPG or type 2 diabetes.

U2 - 10.2337/db09-1757

DO - 10.2337/db09-1757

M3 - Journal article

C2 - 20200315

VL - 59

SP - 1539

EP - 1548

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -

ID: 20943557