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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2010-Jun
OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind59
Udgave nummer6
Sider (fra-til)1539-48
Antal sider9
DOI
StatusUdgivet - 1. jun. 2010

Fingeraftryk

Fasting
Type 2 Diabetes Mellitus
Population
Mutation
COS Cells
Melatonin
Hyperglycemia
Research Design
Odds Ratio

Citer dette

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. I: Diabetes. 2010 ; Bind 59, Nr. 6. s. 1539-48.
@article{6c623a30aa9511dfb62d000ea68e967b,
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.",
keywords = "Age of Onset, Amino Acid Substitution, Blood Glucose, Body Mass Index, Case-Control Studies, Chromosome Mapping, Diabetes Complications, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Fasting, Genetic Variation, Genotype, Glutamate Decarboxylase, Humans, Obesity, Patient Selection, Quantitative Trait Loci, Receptor, Melatonin, MT2",
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 = "6",
day = "1",
doi = "10.2337/db09-1757",
language = "English",
volume = "59",
pages = "1539--48",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "6",

}

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, bind 59, nr. 6, s. 1539-48. https://doi.org/10.2337/db09-1757

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.

I: Diabetes, Bind 59, Nr. 6, 01.06.2010, s. 1539-48.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - 2010/6/1

Y1 - 2010/6/1

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.

KW - Age of Onset

KW - Amino Acid Substitution

KW - Blood Glucose

KW - Body Mass Index

KW - Case-Control Studies

KW - Chromosome Mapping

KW - Diabetes Complications

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Fasting

KW - Genetic Variation

KW - Genotype

KW - Glutamate Decarboxylase

KW - Humans

KW - Obesity

KW - Patient Selection

KW - Quantitative Trait Loci

KW - Receptor, Melatonin, MT2

U2 - 10.2337/db09-1757

DO - 10.2337/db09-1757

M3 - Journal article

VL - 59

SP - 1539

EP - 1548

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -