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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
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2010 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 42, no 2, 142-148 p.Article in journal (Refereed) Published
Abstract [en]

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).

Place, publisher, year, edition, pages
2010. Vol. 42, no 2, 142-148 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-131527DOI: 10.1038/ng.521ISI: 000274084400011PubMedID: 20081857OAI: oai:DiVA.org:uu-131527DiVA: diva2:354762
Available from: 2010-10-04 Created: 2010-10-04 Last updated: 2017-12-12Bibliographically approved

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Ingelsson, ErikSyvänen, Ann-Christine

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