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Nature genetics DOI:10.1038/ng.521

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

Publication TypeJournal Article
Year of Publication2010
AuthorsSaxena, R, Hivert, MF, Langenberg, C, Tanaka, T, Pankow, JS, Vollenweider, P, Lyssenko, V, Bouatia-Naji, N, Dupuis, J, Jackson, AU, Kao, WH, Li, M, Glazer, NL, Manning, AK, Luan, J, Stringham, HM, Prokopenko, I, Johnson, T, Grarup, N, Boesgaard, TW, Lecoeur, C, Shrader, P, O'Connell, J, Ingelsson, E, Couper, DJ, Rice, K, Song, K, Andreasen, CH, 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, MN, Aulchenko, YS, Voight, BF, Grallert, H, Balkau, B, Bergman, RN, Bielinski, SJ, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Böttcher, Y, Brunner, E, Buchanan, TA, Bumpstead, SJ, Cavalcanti-Proença, C, Charpentier, G, Chen, YD, Chines, PS, Collins, FS, Cornelis, M, J Crawford, G, Delplanque, J, Doney, A, Egan, JM, Erdos, MR, Firmann, M, Forouhi, NG, Fox, CS, Goodarzi, MO, Graessler, J, Hingorani, A, Isomaa, B, Jørgensen, T, Kivimaki, M, Kovacs, P, Krohn, K, Kumari, M, Lauritzen, T, Lévy-Marchal, C, Mayor, V, McAteer, JB, Meyre, D, Mitchell, BD, Mohlke, KL, Morken, MA, Narisu, N, Palmer, CN, Pakyz, R, Pascoe, L, Payne, F, Pearson, D, Rathmann, W, Sandbaek, A, Sayer, AA, Scott, LJ, Sharp, SJ, Sijbrands, E, Singleton, A, Siscovick, DS, Smith, NL, Sparsø, T, Swift, AJ, Syddall, H, Thorleifsson, G, Tönjes, A, Tuomi, T, Tuomilehto, J, Valle, TT, Waeber, G, Walley, A, Waterworth, DM, Zeggini, E, Zhao, JH, GIANT, C, investigators MAGIC, , Illig, T, Wichmann, HE, Wilson, JF, van Duijn, C, Hu, FB, Morris, AD, Frayling, TM, Hattersley, AT, Thorsteinsdottir, U, Stefansson, K, Nilsson, P, Syvänen, AC, Shuldiner, AR, Walker, M, Bornstein, SR, Schwarz, P, Williams, GH, Nathan, DM, Kuusisto, J, Laakso, M, Cooper, C, Marmot, M, Ferrucci, L, Mooser, V, Stumvoll, M, Loos, RJ, Altshuler, D, Psaty, BM, Rotter, JI, Boerwinkle, E, Hansen, T, Pedersen, O, Florez, JC, McCarthy, MI, Boehnke, M, Barroso, I, Sladek, R, Froguel, P, Meigs, JB, Groop, L, Wareham, NJ, Watanabe, RM
JournalNature genetics
Volume42
Issue2
Pages142-8
Date Published2010/02/01
ISSN1061-4036
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)).

URLhttp://dx.doi.org/10.1038/ng.521
DOI10.1038/ng.521
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20081857?dopt=Abstract