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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| creator | CHAMBERS, John C WEIHUA ZHANG SCOTT, James ELLIOTT, Paul KOONER, Jaspal S ZABANEH, Delilah SEHMI, Joban JAIN, Piyush MCCARTHY, Mark I FROGUEL, Philippe RUOKONEN, Aimo BALDING, David JARVELIN, Marjo-Riitta |
| description | 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 |
| doi_str_mv | 10.2337/db08-1805 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_journals_216492252</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1902637961</sourcerecordid><originalsourceid>FETCH-LOGICAL-c534t-cb9c18cf95d3fe3d55f1173eb3d5cb516ead24d3c13d5eebec820f72b3fa3acd3</originalsourceid><addsrcrecordid>eNpdkm1rFDEQxxdRbK2-8AtIEEQEV_Ow2Yc3wnnWs1CrHKf4Lswms3epu8mZ7Cr9Un5Gc72jVQkkw39-M5lhJsseM_qKC1G9Ni2tc1ZTeSc7Zo1ocsGrb3ezY0oZz1nVVEfZgxgvKaVlOvezI9aUktWMH2e_534YvCMLdDhaTb5CsDDapFwgBPIRexi9s44sUeN29ElaXSzZWzL3bgy2nUaMZPRkCTaiIZ97iAOQRT9pH5GAM-TM6YCwcy5t_E58R1ZXWyScvLPQ4i58lgpYJ85YcGQW0x2vI0-n4LeYtDlMGq71h9m9DvqIjw7vSfbl_elq_iE__7Q4m8_Ocy1FMea6bTSrdddIIzoURsqOsUpgm0zdSlYiGF4YoVkSEFvUNaddxVvRgQBtxEn2Zp93O7UDGo2pWejVNtgBwpXyYNW_Hmc3au1_Kl6VNZN1SvD8kCD4HxPGUQ02aux7cOinqCpRMFawokzk0__ISz8Fl7pTnJVFw7nkCXqxh3TwMQbsbkphVO12QO12QO12ILFP_q79ljwMPQHPDgBEDX0XwGkbbzjOaV1KSRP3cs9t7HrzywZU5jCyW0OmT1nqmgrxB7g6y9I</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>216492252</pqid></control><display><type>article</type><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</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>CHAMBERS, John C ; WEIHUA ZHANG ; SCOTT, James ; ELLIOTT, Paul ; KOONER, Jaspal S ; ZABANEH, Delilah ; SEHMI, Joban ; JAIN, Piyush ; MCCARTHY, Mark I ; FROGUEL, Philippe ; RUOKONEN, Aimo ; BALDING, David ; JARVELIN, Marjo-Riitta</creator><creatorcontrib>CHAMBERS, John C ; WEIHUA ZHANG ; SCOTT, James ; ELLIOTT, Paul ; KOONER, Jaspal S ; ZABANEH, Delilah ; SEHMI, Joban ; JAIN, Piyush ; MCCARTHY, Mark I ; FROGUEL, Philippe ; RUOKONEN, Aimo ; BALDING, David ; JARVELIN, Marjo-Riitta</creatorcontrib><description>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</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db08-1805</identifier><identifier>PMID: 19651812</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adult ; Aged ; Asian Continental Ancestry Group - genetics ; Asian Continental Ancestry Group - statistics & numerical data ; Asian people ; 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 ; European Continental Ancestry Group - genetics ; European Continental Ancestry Group - statistics & numerical data ; 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</subject><ispartof>Diabetes (New York, N.Y.), 2009-11, Vol.58 (11), p.2703-2708</ispartof><rights>2009 INIST-CNRS</rights><rights>Copyright American Diabetes Association Nov 2009</rights><rights>2009 American Diabetes Association</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-cb9c18cf95d3fe3d55f1173eb3d5cb516ead24d3c13d5eebec820f72b3fa3acd3</citedby><cites>FETCH-LOGICAL-c534t-cb9c18cf95d3fe3d55f1173eb3d5cb516ead24d3c13d5eebec820f72b3fa3acd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768158/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768158/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22086550$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19651812$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHAMBERS, John C</creatorcontrib><creatorcontrib>WEIHUA ZHANG</creatorcontrib><creatorcontrib>SCOTT, James</creatorcontrib><creatorcontrib>ELLIOTT, Paul</creatorcontrib><creatorcontrib>KOONER, Jaspal S</creatorcontrib><creatorcontrib>ZABANEH, Delilah</creatorcontrib><creatorcontrib>SEHMI, Joban</creatorcontrib><creatorcontrib>JAIN, Piyush</creatorcontrib><creatorcontrib>MCCARTHY, Mark I</creatorcontrib><creatorcontrib>FROGUEL, Philippe</creatorcontrib><creatorcontrib>RUOKONEN, Aimo</creatorcontrib><creatorcontrib>BALDING, David</creatorcontrib><creatorcontrib>JARVELIN, Marjo-Riitta</creatorcontrib><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</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>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</description><subject>Adult</subject><subject>Aged</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Asian Continental Ancestry Group - statistics & numerical data</subject><subject>Asian people</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Blood Pressure</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diet</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Environment</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Europe - epidemiology</subject><subject>Europe - ethnology</subject><subject>European Continental Ancestry Group - genetics</subject><subject>European Continental Ancestry Group - statistics & numerical data</subject><subject>Female</subject><subject>Genetic Variation</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Glucose</subject><subject>Humans</subject><subject>Hypertension - epidemiology</subject><subject>Hypertension - genetics</subject><subject>India - epidemiology</subject><subject>India - ethnology</subject><subject>Insulin</subject><subject>Life Style</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melatonin</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Plasma</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptor, Melatonin, MT2 - genetics</subject><subject>Research design</subject><subject>Risk Factors</subject><subject>White people</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkm1rFDEQxxdRbK2-8AtIEEQEV_Ow2Yc3wnnWs1CrHKf4Lswms3epu8mZ7Cr9Un5Gc72jVQkkw39-M5lhJsseM_qKC1G9Ni2tc1ZTeSc7Zo1ocsGrb3ezY0oZz1nVVEfZgxgvKaVlOvezI9aUktWMH2e_534YvCMLdDhaTb5CsDDapFwgBPIRexi9s44sUeN29ElaXSzZWzL3bgy2nUaMZPRkCTaiIZ97iAOQRT9pH5GAM-TM6YCwcy5t_E58R1ZXWyScvLPQ4i58lgpYJ85YcGQW0x2vI0-n4LeYtDlMGq71h9m9DvqIjw7vSfbl_elq_iE__7Q4m8_Ocy1FMea6bTSrdddIIzoURsqOsUpgm0zdSlYiGF4YoVkSEFvUNaddxVvRgQBtxEn2Zp93O7UDGo2pWejVNtgBwpXyYNW_Hmc3au1_Kl6VNZN1SvD8kCD4HxPGUQ02aux7cOinqCpRMFawokzk0__ISz8Fl7pTnJVFw7nkCXqxh3TwMQbsbkphVO12QO12QO12ILFP_q79ljwMPQHPDgBEDX0XwGkbbzjOaV1KSRP3cs9t7HrzywZU5jCyW0OmT1nqmgrxB7g6y9I</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>CHAMBERS, John C</creator><creator>WEIHUA ZHANG</creator><creator>SCOTT, James</creator><creator>ELLIOTT, Paul</creator><creator>KOONER, Jaspal S</creator><creator>ZABANEH, Delilah</creator><creator>SEHMI, Joban</creator><creator>JAIN, Piyush</creator><creator>MCCARTHY, Mark I</creator><creator>FROGUEL, Philippe</creator><creator>RUOKONEN, Aimo</creator><creator>BALDING, David</creator><creator>JARVELIN, Marjo-Riitta</creator><general>American Diabetes Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091101</creationdate><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</title><author>CHAMBERS, John C ; WEIHUA ZHANG ; SCOTT, James ; ELLIOTT, Paul ; KOONER, Jaspal S ; ZABANEH, Delilah ; SEHMI, Joban ; JAIN, Piyush ; MCCARTHY, Mark I ; FROGUEL, Philippe ; RUOKONEN, Aimo ; BALDING, David ; JARVELIN, Marjo-Riitta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-cb9c18cf95d3fe3d55f1173eb3d5cb516ead24d3c13d5eebec820f72b3fa3acd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Asian Continental Ancestry Group - statistics & numerical data</topic><topic>Asian people</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Blood Pressure</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diet</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Environment</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Europe - epidemiology</topic><topic>Europe - ethnology</topic><topic>European Continental Ancestry Group - genetics</topic><topic>European Continental Ancestry Group - statistics & numerical data</topic><topic>Female</topic><topic>Genetic Variation</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genomes</topic><topic>Glucose</topic><topic>Humans</topic><topic>Hypertension - epidemiology</topic><topic>Hypertension - genetics</topic><topic>India - epidemiology</topic><topic>India - ethnology</topic><topic>Insulin</topic><topic>Life Style</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melatonin</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Plasma</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptor, Melatonin, MT2 - genetics</topic><topic>Research design</topic><topic>Risk Factors</topic><topic>White people</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHAMBERS, John C</creatorcontrib><creatorcontrib>WEIHUA ZHANG</creatorcontrib><creatorcontrib>SCOTT, James</creatorcontrib><creatorcontrib>ELLIOTT, Paul</creatorcontrib><creatorcontrib>KOONER, Jaspal S</creatorcontrib><creatorcontrib>ZABANEH, Delilah</creatorcontrib><creatorcontrib>SEHMI, Joban</creatorcontrib><creatorcontrib>JAIN, Piyush</creatorcontrib><creatorcontrib>MCCARTHY, Mark I</creatorcontrib><creatorcontrib>FROGUEL, Philippe</creatorcontrib><creatorcontrib>RUOKONEN, Aimo</creatorcontrib><creatorcontrib>BALDING, David</creatorcontrib><creatorcontrib>JARVELIN, Marjo-Riitta</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHAMBERS, John C</au><au>WEIHUA ZHANG</au><au>SCOTT, James</au><au>ELLIOTT, Paul</au><au>KOONER, Jaspal S</au><au>ZABANEH, Delilah</au><au>SEHMI, Joban</au><au>JAIN, Piyush</au><au>MCCARTHY, Mark I</au><au>FROGUEL, Philippe</au><au>RUOKONEN, Aimo</au><au>BALDING, David</au><au>JARVELIN, Marjo-Riitta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>58</volume><issue>11</issue><spage>2703</spage><epage>2708</epage><pages>2703-2708</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><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</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>19651812</pmid><doi>10.2337/db08-1805</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2009-11, Vol.58 (11), p.2703-2708 |
| issn | 0012-1797 1939-327X |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adult Aged Asian Continental Ancestry Group - genetics Asian Continental Ancestry Group - statistics & numerical data Asian people 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 European Continental Ancestry Group - genetics European Continental Ancestry Group - statistics & numerical data 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 |
| 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 |
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