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Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B
- Hribal, M. L. (author)
- Presta, I. (author)
- Procopio, T. (author)
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- Marini, M. A. (author)
- Stancakova, A. (author)
- Kuusisto, J. (author)
- Andreozzi, F. (author)
- Grarup, N. (author)
- Hansen, T. (author)
- Walker, M. (author)
- Stefan, N. (author)
- Fritsche, A. (author)
- Haring, H. U. (author)
- Pedersen, O. (author)
- Laakso, M. (author)
- Sesti, G. (author)
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- (creator_code:org_t)
- 2011-01-14
- 2011
- English.
- In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 54:4, s. 795-802
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- Beta cell dysfunction; CDKN2A/CDKN2B; Genetics; Insulin; Meta-analysis; Offspring; Type 2 diabetes
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- art (subject category)
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- Hribal, M. L.
- Presta, I.
- Procopio, T.
- Marini, M. A.
- Stancakova, A.
- Kuusisto, J.
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- Andreozzi, F.
- Hammarstedt, Ann ...
- Jansson, Per-And ...
- Grarup, N.
- Hansen, T.
- Walker, M.
- Stefan, N.
- Fritsche, A.
- Haring, H. U.
- Pedersen, O.
- Smith, Ulf, 1943
- Laakso, M.
- Sesti, G.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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- Diabetologia
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- University of Gothenburg
- Karolinska Institutet
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