| Title | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Saxena R, Hivert M-, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, et al. |
| Corporate Authors | GIANT Consortium, MAGIC investigators |
| Journal | Nature genetics |
| Volume | 42 |
| Issue | 2 |
| Pagination | 142-8 |
| Date Published | 2010 Feb |
| ISSN | 1546-1718 |
| Keywords | Adenylate Cyclase, Body Mass Index, Denmark, Diabetes Mellitus, Type 2, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Glucose, Glucose Tolerance Test, Humans, Incretins, Insulin, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Proteins, Receptors, Gastrointestinal Hormone, RNA, Messenger |
| 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)). |
| Alternate Journal | Nat. Genet. |
