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

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Serval ID
serval:BIB_E30C7201086A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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
42
Number
2
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
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2010 15:38
Last modification date
20/08/2019 16:06
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