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

Saxena, R.; Hivert, M.F.; Langenberg, C.; Tanaka, T.; Pankow, J.S.; Vollenweider, P.; Lyssenko, V.; Bouatia-Naji, N.; Dupuis, J.; Jackson, A.U.; Kao, W.H.; Li, M.; Glazer, N.L.; Manning, A.K.; Luan, J.; Stringham, H.M.; Prokopenko, I.; Johnson, T.; Grarup, N.; Boesgaard, T.W.; Lecoeur, C.; Shrader, P.; O'Connell, J.; Ingelsson, E.; Couper, D.J.; Rice, K.; Song, K.; Andreasen, C.H.; Dina, C.; Köttgen, A.; Le Bacquer, O.; Pattou, F.; Taneera, J.; Steinthorsdottir, V.; Rybin, D.; Ardlie, K.; Sampson, M.; Qi, L.; van Hoek, M.; Weedon, M.N.; Aulchenko, Y.S.; Voight, B.F.; Grallert, H.; Balkau, B.; Bergman, R.N.; Bielinski, S.J.; Bonnefond, A.; Bonnycastle, L.L.; Borch-Johnsen, K.; Böttcher, Y.; Brunner, E.; Buchanan, T.A.; Bumpstead, S.J.; Cavalcanti-Proença, C.; Charpentier, G.; Chen, Y.D.; Chines, P.S.; Collins, F.S.; Cornelis, M.; J Crawford, G.; Delplanque, J.; Doney, A.; Egan, J.M.; Erdos, M.R.; Firmann, M.; Forouhi, N.G.; Fox, C.S.; Goodarzi, M.O.; Graessler, J.; Hingorani, A.; Isomaa, B.; Jørgensen, T.; Kivimaki, M.; Kovacs, P.; Krohn, K.; Kumari, M.; Lauritzen, T.; Lévy-Marchal, C.; Mayor, V.; McAteer, J.B.; Meyre, D.; Mitchell, B.D.; Mohlke, K.L.; Morken, M.A.; Narisu, N.; Palmer, C.N.; Pakyz, R.; Pascoe, L.; Payne, F.; Pearson, D.; Rathmann, W.; Sandbaek, A.; Sayer, A.A.; Scott, L.J.; Sharp, S.J.; Sijbrands, E.; Singleton, A.; Siscovick, D.S.; Smith, N.L.; Sparsø, T.; Swift, A.J.; Syddall, H.; Thorleifsson, G.; Tönjes, A.; Tuomi, T.; Tuomilehto, J.; Valle, T.T.; Waeber, G.; Walley, A.; Waterworth, D.M.; Zeggini, E.; Zhao, J.H.; Illig, T.; Illig, T.; Wichmann, H.E.; Wilson, J.F.; van Duijn, C.; Hu, F.B.; Morris, A.D.; Frayling, T.M.; Hattersley, A.T.; Thorsteinsdottir, U.; Stefansson, K.; Nilsson, P.; Syvänen, A.C.; Shuldiner, A.R.; Walker, M.; Bornstein, S.R.; Schwarz, P.; Williams, G.H.; Nathan, D.M.; Kuusisto, J.; Laakso, M.; Cooper, C.; Marmot, M.; Ferrucci, L.; Mooser, V.; Stumvoll, M.; Loos, R.J.; Altshuler, D.; Psaty, B.M.; Rotter, J.I.; Boerwinkle, E.; Hansen, T.; Pedersen, O.; Florez, J.C.; McCarthy, M.I.; Boehnke, M.; Barroso, I.; Sladek, R.; Froguel, P.; Meigs, J.B.; Groop, L.; Wareham, N.J.; Watanabe, R.M.

doi:10.1038/ng.521

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

Details

Download: BIB_E30C7201086A.P001.pdf (2170.20 [Ko])
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Serval ID

serval:BIB_E30C7201086A

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature Genetics

Author(s)

Saxena R., Hivert M.F., Langenberg C., Tanaka T., Pankow J.S., Vollenweider P., Lyssenko V., Bouatia-Naji N., Dupuis J., Jackson A.U., Kao W.H., Li M., Glazer N.L., Manning A.K., Luan J., Stringham H.M., Prokopenko I., Johnson T., Grarup N., Boesgaard T.W., Lecoeur C., Shrader P., O'Connell J., Ingelsson E., Couper D.J., Rice K., Song K., Andreasen C.H., Dina C., Köttgen A., Le Bacquer O., Pattou F., Taneera J., Steinthorsdottir V., Rybin D., Ardlie K., Sampson M., Qi L., van Hoek M., Weedon M.N., Aulchenko Y.S., Voight B.F., Grallert H., Balkau B., Bergman R.N., Bielinski S.J., Bonnefond A., Bonnycastle L.L., Borch-Johnsen K., Böttcher Y., Brunner E., Buchanan T.A., Bumpstead S.J., Cavalcanti-Proença C., Charpentier G., Chen Y.D., Chines P.S., Collins F.S., Cornelis M., J Crawford G., Delplanque J., Doney A., Egan J.M., Erdos M.R., Firmann M., Forouhi N.G., Fox C.S., Goodarzi M.O., Graessler J., Hingorani A., Isomaa B., Jørgensen T., Kivimaki M., Kovacs P., Krohn K., Kumari M., Lauritzen T., Lévy-Marchal C., Mayor V., McAteer J.B., Meyre D., Mitchell B.D., Mohlke K.L., Morken M.A., Narisu N., Palmer C.N., Pakyz R., Pascoe L., Payne F., Pearson D., Rathmann W., Sandbaek A., Sayer A.A., Scott L.J., Sharp S.J., Sijbrands E., Singleton A., Siscovick D.S., Smith N.L., Sparsø T., Swift A.J., Syddall H., Thorleifsson G., Tönjes A., Tuomi T., Tuomilehto J., Valle T.T., Waeber G., Walley A., Waterworth D.M., Zeggini E., Zhao J.H., Illig T., Illig T., Wichmann H.E., Wilson J.F., van Duijn C., Hu F.B., Morris A.D., Frayling T.M., Hattersley A.T., Thorsteinsdottir U., Stefansson K., Nilsson P., Syvänen A.C., Shuldiner A.R., Walker M., Bornstein S.R., Schwarz P., Williams G.H., Nathan D.M., Kuusisto J., Laakso M., Cooper C., Marmot M., Ferrucci L., Mooser V., Stumvoll M., Loos R.J., Altshuler D., Psaty B.M., Rotter J.I., Boerwinkle E., Hansen T., Pedersen O., Florez J.C., McCarthy M.I., Boehnke M., Barroso I., Sladek R., Froguel P., Meigs J.B., Groop L., Wareham N.J., Watanabe R.M.

Working group(s)

GIANT consortium, MAGIC investigators

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

2010

Peer-reviewed

Oui

Volume

Number

Pages

142-148

Language

english

Abstract

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)).

Keywords

Adenylate Cyclase/genetics, Body Mass Index, Type="Geographic">Denmark, Diabetes Mellitus, Type 2/genetics, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Loci/genetics, Genetic Variation, Genome-Wide Association Study, Glucose/metabolism, Glucose Tolerance Test, Humans, Incretins/genetics, Insulin/metabolism, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide/genetics, Proteins/genetics, RNA, Messenger/genetics, RNA, Messenger/metabolism, Receptors, Gastrointestinal Hormone/genetics, Receptors, Gastrointestinal Hormone/metabolism , Colaus Study

URN

urn:nbn:ch:serval-BIB_E30C7201086A6

OAI-PMH

oai:serval.unil.ch:BIB_E30C7201086A

DOI

10.1038/ng.521

Pubmed

20081857

Web of science

000274084400011

Open Access

Yes