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Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

Lookup NU author(s): Professor Mark Walker


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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. 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. 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). 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.

Publication metadata

Author(s): Hribal ML, Presta I, Procopio T, Marini MA, Stancakova A, Kuusisto J, Andreozzi F, Hammarstedt A, Jansson PA, Grarup N, Hansen T, Walker M, Stefan N, Fritsche A, Haring HU, Pedersen O, Smith U, Laakso M, Sesti G, on behalf of the EUGENE2 Consortium

Publication type: Article

Publication status: Published

Journal: Diabetologia

Year: 2011

Volume: 54

Issue: 4

Pages: 795-802

Print publication date: 14/01/2011

ISSN (print): 0012-186X

ISSN (electronic): 1432-0428

Publisher: Springer


DOI: 10.1007/s00125-010-2038-8


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Funder referenceFunder name
LSHM-CT-2004-512013European Community