Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians

Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians John C. Chambers 1 , Weihua Zhang 1 , Delilah Zabaneh 1 , Joban Sehmi 2 , Piyush Jain 2 , Mark I. McCarthy 3 , Philippe Frogu...

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Veröffentlicht in:Diabetes (New York, N.Y.) Jg. 58; H. 11; S. 2703 - 2708
Hauptverfasser: Chambers, John C., Zhang, Weihua, Zabaneh, Delilah, Sehmi, Joban, Jain, Piyush, McCarthy, Mark I., Froguel, Philippe, Ruokonen, Aimo, Balding, David, Jarvelin, Marjo-Riitta, Scott, James, Elliott, Paul, Kooner, Jaspal S.
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Sprache:Englisch
Veröffentlicht: Alexandria, VA American Diabetes Association 01.11.2009
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ISSN:0012-1797, 1939-327X, 1939-327X
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Abstract Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians John C. Chambers 1 , Weihua Zhang 1 , Delilah Zabaneh 1 , Joban Sehmi 2 , Piyush Jain 2 , Mark I. McCarthy 3 , Philippe Froguel 4 , 5 , Aimo Ruokonen 6 , David Balding 1 , Marjo-Riitta Jarvelin 1 , 7 , James Scott 2 , Paul Elliott 1 and Jaspal S. Kooner 2 1 Department of Epidemiology and Public Health, Imperial College London, London, U.K.; 2 National Heart and Lung Institute, Imperial College London, London, U.K.; 3 Oxford Centre for Diabetes, Endocrinology and Metabolism and Oxford National Institute for Health Research, Biomedical Research Centre, Oxford, U.K.; 4 Section of Genomic Medicine, Imperial College London, London, U.K., and the Centre National de la Recherche Scientifique, 8090-Institute of Biology, Pasteur Institute, Lille, France; 5 UMR 8090-Institute of Biology, Pasteur Institute, Lille, France; 6 Department of Clinical Sciences/Clinical Chemistry, University Hospital Oulu, Oulu, Finland; 7 Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland, and Department of Child and Adolescent Health, National Institute of Health and Welfare, Helsinki, Finland. Corresponding author: Jaspal S. Kooner, j.kooner{at}imperial.ac.uk . Abstract OBJECTIVE Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians. RESEARCH DESIGN AND METHODS We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians. RESULTS We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 × 10 −8 , all near melatonin receptor MTNR1B . The most closely associated was rs2166706 (combined P = 2.1 × 10 −9 ), which is in moderate linkage disequilibrium with rs1387153 ( r 2 = 0.60) and rs10830963 ( r 2 = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively ( P = 0.44); effect 0.05 (95% CI 0.01–0.08) versus 0.05 (0.03–0.07 mmol/l), respectively, higher glucose per allele copy ( P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06–1.38] per copy of risk allele; P = 0.006). SNPs at the GCK , GCKR , and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 ( GCKR ) and rs560887 ( G6PC2 ) were higher among Indian Asians compared with European Caucasians. CONCLUSIONS Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B , GCK , GCKR , and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received December 29, 2008. Accepted July 13, 2009. © 2009 American Diabetes Association
AbstractList Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians John C. Chambers 1 , Weihua Zhang 1 , Delilah Zabaneh 1 , Joban Sehmi 2 , Piyush Jain 2 , Mark I. McCarthy 3 , Philippe Froguel 4 , 5 , Aimo Ruokonen 6 , David Balding 1 , Marjo-Riitta Jarvelin 1 , 7 , James Scott 2 , Paul Elliott 1 and Jaspal S. Kooner 2 1 Department of Epidemiology and Public Health, Imperial College London, London, U.K.; 2 National Heart and Lung Institute, Imperial College London, London, U.K.; 3 Oxford Centre for Diabetes, Endocrinology and Metabolism and Oxford National Institute for Health Research, Biomedical Research Centre, Oxford, U.K.; 4 Section of Genomic Medicine, Imperial College London, London, U.K., and the Centre National de la Recherche Scientifique, 8090-Institute of Biology, Pasteur Institute, Lille, France; 5 UMR 8090-Institute of Biology, Pasteur Institute, Lille, France; 6 Department of Clinical Sciences/Clinical Chemistry, University Hospital Oulu, Oulu, Finland; 7 Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland, and Department of Child and Adolescent Health, National Institute of Health and Welfare, Helsinki, Finland. Corresponding author: Jaspal S. Kooner, j.kooner{at}imperial.ac.uk . Abstract OBJECTIVE Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians. RESEARCH DESIGN AND METHODS We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians. RESULTS We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 × 10 −8 , all near melatonin receptor MTNR1B . The most closely associated was rs2166706 (combined P = 2.1 × 10 −9 ), which is in moderate linkage disequilibrium with rs1387153 ( r 2 = 0.60) and rs10830963 ( r 2 = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively ( P = 0.44); effect 0.05 (95% CI 0.01–0.08) versus 0.05 (0.03–0.07 mmol/l), respectively, higher glucose per allele copy ( P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06–1.38] per copy of risk allele; P = 0.006). SNPs at the GCK , GCKR , and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 ( GCKR ) and rs560887 ( G6PC2 ) were higher among Indian Asians compared with European Caucasians. CONCLUSIONS Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B , GCK , GCKR , and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received December 29, 2008. Accepted July 13, 2009. © 2009 American Diabetes Association
Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians. We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians. We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x 10(-8), all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x 10(-9)), which is in moderate linkage disequilibrium with rs1387153 (r(2) = 0.60) and rs10830963 (r(2) = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians. Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.
Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians. We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians. We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x 10(-8), all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x 10(-9)), which is in moderate linkage disequilibrium with rs1387153 (r(2) = 0.60) and rs10830963 (r(2) = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians. Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.
Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians.OBJECTIVEFasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians.We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians.RESEARCH DESIGN AND METHODSWe carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians.We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x 10(-8), all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x 10(-9)), which is in moderate linkage disequilibrium with rs1387153 (r(2) = 0.60) and rs10830963 (r(2) = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians.RESULTSWe identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x 10(-8), all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x 10(-9)), which is in moderate linkage disequilibrium with rs1387153 (r(2) = 0.60) and rs10830963 (r(2) = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians.Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.CONCLUSIONSCommon genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.
Author Jaspal S. Kooner
Marjo-Riitta Jarvelin
Weihua Zhang
Paul Elliott
Piyush Jain
James Scott
Mark I. McCarthy
David Balding
Delilah Zabaneh
John C. Chambers
Joban Sehmi
Philippe Froguel
Aimo Ruokonen
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  organization: Department of Epidemiology and Public Health, Imperial College London, London, U.K
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  surname: Jarvelin
  fullname: Jarvelin, Marjo-Riitta
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  organization: National Heart and Lung Institute, Imperial College London, London, U.K
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ContentType Journal Article
Copyright 2009 INIST-CNRS
Copyright American Diabetes Association Nov 2009
2009 American Diabetes Association
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Issue 11
Keywords Endocrinopathy
Type 2 diabetes
Melatonin
Risk factor
Metabolic diseases
Genetics
Indian
Glucose
Pineal hormone
Biological receptor
Language English
License CC BY 4.0
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
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PublicationTitle Diabetes (New York, N.Y.)
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Snippet Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and...
Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have...
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StartPage 2703
SubjectTerms Adult
Aged
Asian people
Asian People - genetics
Asian People - statistics & numerical data
Biological and medical sciences
Blood Glucose - metabolism
Blood Pressure
Diabetes
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
Diabetes. Impaired glucose tolerance
Diet
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Environment
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Europe - epidemiology
Europe - ethnology
Female
Genetic Variation
Genome-Wide Association Study - methods
Genomes
Glucose
Humans
Hypertension - epidemiology
Hypertension - genetics
India - epidemiology
India - ethnology
Insulin
Life Style
Male
Medical sciences
Melatonin
Metabolism
Middle Aged
Original
Plasma
Polymorphism, Single Nucleotide
Receptor, Melatonin, MT2 - genetics
Research design
Risk Factors
White people
White People - genetics
White People - statistics & numerical data
Title Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians
URI http://diabetes.diabetesjournals.org/content/58/11/2703.abstract
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