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Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism.
Monday,2013-01-14 17:08 America/Los_Angeles — poolea2
| Title | Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Walford, GA, Green, T, Neale, B, Isakova, T, Rotter, JI, Grant, SFA, Fox, CS, Pankow, JS, Wilson, JG, Meigs, JB, Siscovick, DS, Bowden, DW, Daly, MJ, Florez, JC |
| Journal | Diabetologia |
| Volume | 55 |
| Issue | 2 |
| Pagination | 331-9 |
| Date Published | 2012 Feb |
| ISSN | 1432-0428 |
| Keywords | Adult, Aged, Blood Glucose, Cohort Studies, Diabetes Mellitus, Type 2, Disease Progression, Fasting, Female, Genetic Variation, Genotype, Humans, Male, Middle Aged, Models, Genetic, Polymorphism, Single Nucleotide, Proportional Hazards Models, Regression Analysis, Risk |
| Abstract | <p><b>AIMS/HYPOTHESIS: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS/INTERPRETATION: </b>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.</p> |
| DOI | 10.1007/s00125-011-2353-8 |
| Alternate Journal | Diabetologia |
| PubMed ID | 22038522 |
| PubMed Central ID | PMC3589986 |
| Grant List | R01 DK078616 / DK / NIDDK NIH HHS / United States DK007028 / DK / NIDDK NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States K24 DK080140 / DK / NIDDK NIH HHS / United States UL1 RR025758 / RR / NCRR NIH HHS / United States K23 DK087858 / DK / NIDDK NIH HHS / United States |