| Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism. | |
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MedLine Citation:
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PMID: 22038522 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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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Authors:
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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 |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-29 |
Journal Detail:
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Title: Diabetologia Volume: - ISSN: 1432-0428 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Center for Human Genetic Research, Simches Research Building-CPZN 5.250, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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