G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans
| Autor: | Sparso, T, Bonnefond, A, Andersson, E, Bouatia-Naji, N, Holmkvist, J, Wegner, L, Grarup, N, Gjesing, AP, Banasik, K, Cavalcanti-Proenca, C, Marchand, M, Vaxillaire, M, Charpentier, G, Jarvelin, M-R, Tichet, J, Balkau, B, Marre, M, Levy-Marchal, C, Faerch, K, Borch-Johnsen, K, Jorgensen, T, Madsbad, S, Poulsen, P, Vaag, A, Dina, C, Hansen, T, Pedersen, O, Froguel, P |
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| Přispěvatelé: | Medical Research Council (MRC) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Blood Glucose endocrine system diseases Denmark VARIANT European Continental Ancestry Group Quantitative Trait Loci Twins MELATONIN RECEPTORS White People Endocrinology & Metabolism BETA-CELL FUNCTION Risk Factors Insulin-Secreting Cells Insulin Secretion Genetics Humans Insulin TOLERANCE POPULATION 11 Medical and Health Sciences Aged Science & Technology ROLES Receptor Melatonin MT1 nutritional and metabolic diseases Genetic Variation Introns Glucose Diabetes Mellitus Type 2 Liver YOUNG SECRETION SENSITIVITY Insulin Resistance Life Sciences & Biomedicine |
| Zdroj: | Sparsø, T, Bonnefond, A, Andersson, E, Bouatia-Naji, N, Holmkvist, J, Wegner, L, Grarup, N, Gjesing, A P, Banasik, K, Cavalcanti-Proença, C, Marchand, M, Vaxillaire, M, Charpentier, G, Jarvelin, M-R, Tichet, J, Balkau, B, Marre, M, Lévy-Marchal, C, Faerch, K, Borch-Johnsen, K, Jørgensen, T, Madsbad, S, Poulsen, P, Vaag, A, Dina, C, Hansen, T, Pedersen, O & Froguel, P 2009, ' G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans ', Diabetes, vol. 58, no. 6, pp. 1450-6 . https://doi.org/10.2337/db08-1660 Diabetes |
| Popis: | Udgivelsesdato: 2009-Jun OBJECTIVE: Genome-wide association studies have identified several variants within the MTNR1B locus that are associated with fasting plasma glucose (FPG) and type 2 diabetes. We refined the association signal by direct genotyping and examined for associations of the variant displaying the most independent effect on FPG with isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), type 2 diabetes, and measures of insulin release and peripheral and hepatic insulin sensitivity. RESEARCH DESIGN AND METHODS: We examined European-descent participants in the Inter99 study (n = 5,553), in a sample of young healthy Danes (n = 372), in Danish twins (n = 77 elderly and n = 97 young), in additional Danish type 2 diabetic patients (n = 1,626) and control subjects (n = 505), in the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study (n = 4,656), in the North Finland Birth Cohort 86 (n = 5,258), and in the Haguenau study (n = 1,461). RESULTS: The MTNR1B intronic variant, rs10830963, carried most of the effect on FPG and showed the strongest association with FPG (combined P = 5.3 x 10(-31)) and type 2 diabetes. The rs10830963 G-allele increased the risk of i-IFG (odds ratio [OR] 1.64, P = 5.5 x 10(-11)) but not i-IGT. The G-allele was associated with a decreased insulin release after oral and intravenous glucose challenges (P < 0.01) but not after injection of tolbutamide. In elderly twins, the G-allele associated with hepatic insulin resistance (P = 0.017). CONCLUSIONS: The G-allele of MTNR1B rs10830963 increases risk of type 2 diabetes through a state of i-IFG and not through i-IGT. The same allele associates with estimates of beta-cell dysfunction and hepatic insulin resistance. |
| Databáze: | OpenAIRE |
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