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01.02.2012 | Article

Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism

verfasst von: G. A. Walford, T. Green, B. Neale, T. Isakova, J. I. Rotter, S. F. A. Grant, C. S. Fox, J. S. Pankow, J. G. Wilson, J. B. Meigs, D. S. Siscovick, D. W. Bowden, M. J. Daly, J. C. Florez

Erschienen in: Diabetologia | Ausgabe 2/2012

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Abstract

Aims/hypothesis

Common genetic variants have been associated with type 2 diabetes. We hypothesised that a subset of these variants may have different effects on the transition from normal fasting glucose (NFG) to impaired fasting glucose (IFG) than on that from IFG to diabetes.

Methods

We identified 16 type 2 diabetes risk variants from the Illumina Broad Candidate-gene Association Resource (CARe) array genotyped in 26,576 CARe participants. Participants were categorised at baseline as NFG, IFG or type 2 diabetic (n = 16,465, 8,017 or 2,291, respectively). Using Cox proportional hazards and likelihood ratio tests (LRTs), we compared rates of progression by genotype for 4,909 (NFG to IFG) and 1,518 (IFG to type 2 diabetes) individuals, respectively. We then performed multinomial regression analyses at baseline, comparing the risk of assignment to the NFG, IFG or diabetes groups by genotype.

Results

The rate of progression from NFG to IFG was significantly greater in participants carrying the risk allele at MTNR1B (p = 1 × 10⁻⁴), nominally greater at GCK and SLC30A8 (p < 0.05) and nominally smaller at IGF2BP2 (p = 0.01) than the rate of progression from IFG to diabetes by the LRT. Results of the baseline, multinomial regression model were consistent with these findings.

Conclusions/interpretation

Common genetic risk variants at GCK, SLC30A8, IGF2BP2 and MTNR1B influence to different extents the development of IFG and the transition from IFG to type 2 diabetes. Our findings may have implications for understanding the genetic contribution of these variants to the development of IFG and type 2 diabetes.

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Titel: Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism
verfasst von: G. A. Walford
T. Green
B. Neale
T. Isakova
J. I. Rotter
S. F. A. Grant
C. S. Fox
J. S. Pankow
J. G. Wilson
J. B. Meigs
D. S. Siscovick
D. W. Bowden
M. J. Daly
J. C. Florez
Publikationsdatum: 01.02.2012
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 2/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2353-8

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Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism