Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

被引：486

作者：

Saxena, Richa ^{[2
,3
]}

Hivert, Marie-France ^{[4
,5
]}

Langenberg, Claudia ^{[6
]}

Tanaka, Toshiko ^{[7
,8
]}

Pankow, James S. ^{[9
]}

Vollenweider, Peter ^{[10
]}

Lyssenko, Valeriya ^{[11
]}

Bouatia-Naji, Nabila ^{[12
]}

Dupuis, Josee ^{[13
]}

Jackson, Anne U. ^{[14
]}

Kao, W. H. Linda ^{[15
,16
,17
]}

Li, Man ^{[15
]}

Glazer, Nicole L. ^{[18
,19
]}

Manning, Alisa K. ^{[13
]}

Luan, Jian'an ^{[6
]}

Stringham, Heather M. ^{[14
]}

Prokopenko, Inga ^{[20
,21
]}

Johnson, Toby ^{[22
]}

Grarup, Niels ^{[23
]}

Boesgaard, Trine W. ^{[23
]}

Lecoeur, Cecile ^{[12
]}

Shrader, Peter ^{[4
]}

O'Connell, Jeffrey ^{[24
]}

Ingelsson, Erik ^{[25
,26
]}

Couper, David J. ^{[27
]}

Rice, Kenneth ^{[28
]}

Song, Kijoung ^{[29
]}

Andreasen, Camilla H. ^{[23
]}

Dina, Christian ^{[12
]}

Koettgen, Anna ^{[15
]}

Le Bacquer, Olivier ^{[12
]}

Pattou, Francois ^{[30
,31
]}

Taneera, Jalal ^{[11
]}

Steinthorsdottir, Valgerdur ^{[32
]}

Rybin, Denis ^{[33
]}

Ardlie, Kristin

Sampson, Michael ^{[34
]}

Qi, Lu ^{[35
,36
]}

van Hoek, Mandy ^{[37
]}

Weedon, Michael N. ^{[38
]}

Aulchenko, Yurii S. ^{[39
]}

Voight, Benjamin F. ^{[2
,3
]}

Grallert, Harald ^{[40
]}

Balkau, Beverley ^{[41
,42
]}

Bergman, Richard N. ^{[1
]}

Bielinski, Suzette J. ^{[43
]}

Bonnefond, Amelie ^{[12
]}

Bonnycastle, Lori L. ^{[44
]}

Borch-Johnsen, Knut ^{[45
,46
]}

Boettcher, Yvonne ^{[47
]}

机构：

[1] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA

[2] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA

[5] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[6] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England

[7] Medstar Res Inst, Baltimore, MD USA

[8] NIA, Clin Res Branch, Baltimore, MD 21224 USA

[9] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[10] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland

[11] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden

[12] Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France

[13] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[14] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[15] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[16] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[17] Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA

[18] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[19] Univ Washington, Dept Med, Seattle, WA USA

[20] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[21] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[22] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[23] Hagedorn Res Inst, Gentofte, Denmark

[24] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[25] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[26] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden

[27] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA

[28] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[29] GlaxoSmithKline Inc, Drug Discovery, Genet, King Of Prussia, PA USA

[30] Univ Lille Nord France, INSERM, Lille, France

[31] Ctr Hosp Reg & Univ Lille, F-59037 Lille, France

[32] deCODE Genet, Reykjavik, Iceland

[33] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA

[34] Norfolk & Norwich Univ Hosp Natl Hlth Serv Trust, Dept Endocrinol & Diabet, Norwich, Norfolk, England

[35] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[36] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[37] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[38] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England

[39] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, NL-3000 DR Rotterdam, Netherlands

[40] Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany

[41] INSERM, Villejuif, France

[42] Univ Paris 11, Orsay, France

[43] Mayo Clin, Coll Med, Rochester, MN USA

[44] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA

[45] Steno Diabet Ctr, Copenhagen, Denmark

[46] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark

[47] Univ Leipzig, Dept Med, Leipzig, Germany

[48] UCL, Dept Epidemiol & Publ Hlth, London, England

[49] Univ So Calif, Keck Sch Med, Div Endocrinol, Dept Med, Los Angeles, CA 90033 USA

[50] Wellcome Trust Sanger Inst, Cambridge, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 02期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

FASTING PLASMA-GLUCOSE; GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; BETA-CELL FUNCTION; ASSOCIATION; RISK; RECEPTOR; SENSITIVITY; EXPRESSION; VARIANTS;

D O I：

10.1038/ng.521

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

引用

页码：142 / U75

页数：9

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