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

Ehm A Andersson; Birgitte Holst; Thomas Sparsø; Niels Grarup; Karina Banasik; Johan Holmkvist; Torben Jørgensen; Knut Borch-Johnsen; Kristoffer L Egerod; Torsten Lauritzen; Thorkild I A Sørensen; Amélie Bonnefond; David Meyre; Philippe Froguel; Thue W Schwartz; Oluf Pedersen; Torben Hansen

doi:10.2337/db09-1757

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

Ehm A Andersson, Birgitte Holst, Thomas Sparsø, Niels Grarup, Karina Banasik, Johan Holmkvist, Torben Jørgensen, Knut Borch-Johnsen, Kristoffer L Egerod, Torsten Lauritzen, Thorkild I A Sørensen, Amélie Bonnefond, David Meyre, Philippe Froguel, Thue W Schwartz, Oluf Pedersen, Torben Hansen

36 Citations (Scopus)

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 × 10^-4) and increased BMI (β = 0.5 kg/m²; P = 1.2 × 10^-5) and waist circumference (β = 1.2 cm; P = 9 × 10^-6) in combined Danish and French study samples. 24E also associated with decreased FPG (β = -0.08 mmol/l; P = 9.2 × 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.

Original language	English
Journal	Diabetes
Volume	59
Issue number	6
Pages (from-to)	1539-48
Number of pages	10
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db09-1757
Publication status	Published - Jun 2010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.2337/db09-1757

Cite this

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

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

@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 × 10-4) and increased BMI (β = 0.5 kg/m2; P = 1.2 × 10-5) and waist circumference (β = 1.2 cm; P = 9 × 10-6) in combined Danish and French study samples. 24E also associated with decreased FPG (β = -0.08 mmol/l; P = 9.2 × 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",

month = jun,

doi = "10.2337/db09-1757",

language = "English",

volume = "59",

pages = "1539--48",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "6",

}

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 - 2010/6

Y1 - 2010/6

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 × 10-4) and increased BMI (β = 0.5 kg/m2; P = 1.2 × 10-5) and waist circumference (β = 1.2 cm; P = 9 × 10-6) in combined Danish and French study samples. 24E also associated with decreased FPG (β = -0.08 mmol/l; P = 9.2 × 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 × 10-4) and increased BMI (β = 0.5 kg/m2; P = 1.2 × 10-5) and waist circumference (β = 1.2 cm; P = 9 × 10-6) in combined Danish and French study samples. 24E also associated with decreased FPG (β = -0.08 mmol/l; P = 9.2 × 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

SN - 0012-1797

VL - 59

SP - 1539

EP - 1548

JO - Diabetes

JF - Diabetes

IS - 6

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this