Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge Academic Article uri icon

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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)).

authors

  • Saxena, Richa
  • Hivert, Marie-France
  • Langenberg, Claudia
  • Tanaka, Toshiko
  • Pankow, James S
  • Vollenweider, Peter
  • Lyssenko, Valeriya
  • Bouatia-Naji, Nabila
  • Dupuis, Josée
  • Jackson, Anne U
  • Kao, WH Linda
  • Li, Man
  • Glazer, Nicole L
  • Manning, Alisa K
  • Luan, Jian'an
  • Stringham, Heather M
  • Prokopenko, Inga
  • Johnson, Toby
  • Grarup, Niels
  • Boesgaard, Trine W
  • Lecoeur, Cécile
  • Shrader, Peter
  • O'Connell, Jeffrey
  • Ingelsson, Erik
  • Couper, David J
  • Rice, Kenneth
  • Song, Kijoung
  • Andreasen, Camilla H
  • Dina, Christian
  • Köttgen, Anna
  • Le Bacquer, Olivier
  • Pattou, François
  • Taneera, Jalal
  • Steinthorsdottir, Valgerdur
  • Rybin, Denis
  • Ardlie, Kristin
  • Sampson, Michael
  • Qi, Lu
  • van Hoek, Mandy
  • Weedon, Michael N
  • Aulchenko, Yurii S
  • Voight, Benjamin F
  • Grallert, Harald
  • Balkau, Beverley
  • Bergman, Richard N
  • Bielinski, Suzette J
  • Bonnefond, Amelie
  • Bonnycastle, Lori L
  • Borch-Johnsen, Knut
  • Böttcher, Yvonne
  • Brunner, Eric
  • Buchanan, Thomas A
  • Bumpstead, Suzannah J
  • Cavalcanti-Proença, Christine
  • Charpentier, Guillaume
  • Chen, Yii-Der Ida
  • Chines, Peter S
  • Collins, Francis S
  • Cornelis, Marilyn
  • J Crawford, Gabriel
  • Delplanque, Jerome
  • Doney, Alex
  • Egan, Josephine M
  • Erdos, Michael R
  • Firmann, Mathieu
  • Forouhi, Nita G
  • Fox, Caroline S
  • Goodarzi, Mark O
  • Graessler, Jürgen
  • Hingorani, Aroon
  • Isomaa, Bo
  • Jørgensen, Torben
  • Kivimaki, Mika
  • Kovacs, Peter
  • Krohn, Knut
  • Kumari, Meena
  • Lauritzen, Torsten
  • Lévy-Marchal, Claire
  • Mayor, Vladimir
  • McAteer, Jarred B
  • Meyre, David Jean-Claude
  • Mitchell, Braxton D
  • Mohlke, Karen L
  • Morken, Mario A
  • Narisu, Narisu
  • Palmer, Colin NA
  • Pakyz, Ruth
  • Pascoe, Laura
  • Payne, Felicity
  • Pearson, Daniel
  • Rathmann, Wolfgang
  • Sandbaek, Annelli
  • Sayer, Avan Aihie
  • Scott, Laura J
  • Sharp, Stephen J
  • Sijbrands, Eric
  • Singleton, Andrew
  • Siscovick, David S
  • Smith, Nicholas L
  • Sparsø, Thomas
  • Swift, Amy J
  • Syddall, Holly
  • Thorleifsson, Gudmar
  • Tönjes, Anke
  • Tuomi, Tiinamaija
  • Tuomilehto, Jaakko
  • Valle, Timo T
  • Waeber, Gérard
  • Walley, Andrew
  • Waterworth, Dawn M
  • Zeggini, Eleftheria
  • Zhao, Jing Hua

publication date

  • February 2010

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