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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)331-339
Number of pages9
JournalDiabetologia
Volume55
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Common genetic variants
  • Diabetes mellitus
  • Genetics
  • Glycaemic progression
  • Impaired fasting glucose
  • Normal fasting glucose
  • Single nucleotide polymorphism
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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