Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B
| Autor: | Hribal ML, Presta I, Procopio T, Marini MA, Stančáková A, Kuusisto J, Andreozzi F, Hammarstedt A, Jansson PA, Grarup N, Hansen T, Walker M, Stefan N, Fritsche A, Häring HU, Pedersen O, Smith U, Laakso M, Sesti G, Haring H, Zierath J, Joost HG, BEGUINOT, FRANCESCO, van Obberghen E, Auwerx J, Bosch F, Lind P. |
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| Přispěvatelé: | Hribal, Ml, Presta, I, Procopio, T, Marini, Ma, Stančáková, A, Kuusisto, J, Andreozzi, F, Hammarstedt, A, Jansson, Pa, Grarup, N, Hansen, T, Walker, M, Stefan, N, Fritsche, A, Häring, Hu, Pedersen, O, Smith, U, Laakso, M, Sesti, G, Haring, H, Zierath, J, Joost, Hg, Beguinot, Francesco, van Obberghen, E, Auwerx, J, Bosch, F, Lind, P. |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Settore MED/09 - Medicina Interna Offspring Endocrinology Diabetes and Metabolism medicine.medical_treatment Type 2 diabetes Biology Impaired glucose tolerance Genetic Polymorphism (computer science) Internal medicine Insulin Secretion Genotype Diabetes Mellitus Internal Medicine medicine Humans Insulin Genetic Predisposition to Disease Polymorphism Allele Cyclin-Dependent Kinase Inhibitor p16 Pancreatic hormone Cyclin-Dependent Kinase Inhibitor p15 Polymorphism Genetic Middle Aged Female Insulin Resistance Diabetes Mellitus Type 2 Sequence Analysis DNA DNA medicine.disease Endocrinology Sequence Analysis Type 2 |
| Zdroj: | Hribal, M L, Presta, I, Procopio, T, Marini, M A, Stancakova, A, Kuusisto, J, Andreozzi, F, Hammarstedt, A, Jansson, P A, Grarup, N, Hansen, T, Walker, M, Stefan, N, Fritsche, A, Haring, H U, Pedersen, O, Smith, U, Laakso, M, Sesti, G & Consortium, E 2011, ' Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B ', Diabetologia, vol. 54, no. 4, pp. 795-802 . https://doi.org/10.1007/s00125-010-2038-8 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-010-2038-8 |
| Popis: | AIMS/HYPOTHESIS: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. METHODS: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. RESULTS: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p = 0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p = 0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). CONCLUSIONS/INTERPRETATION: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function. |
| Databáze: | OpenAIRE |
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