Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.
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). W...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1797084516051845120 |
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| author | Saxena, R Hivert, M Langenberg, C Tanaka, T Pankow, J Vollenweider, P Lyssenko, V Bouatia-Naji, N Dupuis, J Jackson, A Kao, W Li, M Glazer, N Manning, A Luan, J Stringham, H Prokopenko, I Johnson, T Grarup, N Boesgaard, T Lecoeur, C Shrader, P O'Connell, J Ingelsson, E Couper, D |
| author_facet | Saxena, R Hivert, M Langenberg, C Tanaka, T Pankow, J Vollenweider, P Lyssenko, V Bouatia-Naji, N Dupuis, J Jackson, A Kao, W Li, M Glazer, N Manning, A Luan, J Stringham, H Prokopenko, I Johnson, T Grarup, N Boesgaard, T Lecoeur, C Shrader, P O'Connell, J Ingelsson, E Couper, D |
| author_sort | Saxena, R |
| collection | OXFORD |
| description | 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)). |
| first_indexed | 2024-03-07T01:56:11Z |
| format | Journal article |
| id | oxford-uuid:9bc8efe0-eaab-44e8-b456-f4cc1b60a2de |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:56:11Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:9bc8efe0-eaab-44e8-b456-f4cc1b60a2de2022-03-27T00:31:22ZGenetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9bc8efe0-eaab-44e8-b456-f4cc1b60a2deEnglishSymplectic Elements at Oxford2010Saxena, RHivert, MLangenberg, CTanaka, TPankow, JVollenweider, PLyssenko, VBouatia-Naji, NDupuis, JJackson, AKao, WLi, MGlazer, NManning, ALuan, JStringham, HProkopenko, IJohnson, TGrarup, NBoesgaard, TLecoeur, CShrader, PO'Connell, JIngelsson, ECouper, DGlucose 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)). |
| spellingShingle | Saxena, R Hivert, M Langenberg, C Tanaka, T Pankow, J Vollenweider, P Lyssenko, V Bouatia-Naji, N Dupuis, J Jackson, A Kao, W Li, M Glazer, N Manning, A Luan, J Stringham, H Prokopenko, I Johnson, T Grarup, N Boesgaard, T Lecoeur, C Shrader, P O'Connell, J Ingelsson, E Couper, D Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| title | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| title_full | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| title_fullStr | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| title_full_unstemmed | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| title_short | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| title_sort | genetic variation in gipr influences the glucose and insulin responses to an oral glucose challenge |
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