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- Title
Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.
- 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.; Linda Kao, W. H.; Man Li; Glazer, Nicole L.; Manning, Alisa K.; Jian'an Luan; Stringham, Heather M.; Prokopenko, Inga; Johnson, Toby; Grarup, Niels; Boesgaard, Trine W.
- 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, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 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 × 10−18).
- Subjects
GLUCOSE tolerance tests; TYPE 2 diabetes diagnosis; GENOMES; INSULIN; MESSENGER RNA; HYPERGLYCEMIA
- Publication
Nature Genetics, 2010, Vol 42, Issue 2, p142
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.521