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. 2010 Aug;20(4):310-8.
doi: 10.1016/j.ghir.2010.04.002.

IGF2BP1, IGF2BP2 and IGF2BP3 Genotype, Haplotype and Genetic Model Studies in Metabolic Syndrome Traits and Diabetes

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Free PMC article

IGF2BP1, IGF2BP2 and IGF2BP3 Genotype, Haplotype and Genetic Model Studies in Metabolic Syndrome Traits and Diabetes

S Rodriguez et al. Growth Horm IGF Res. .
Free PMC article

Abstract

Objective: Genetic variation at the insulin-like binding protein 2 (IGF2BP2) gene has been associated with type 2 diabetes (T2D) by genome-wide association studies and by replication analyses. Our aim was to explore the underlying genetic model and mechanism of action, factors accounting for non-replications of the associations, and the effect of variation from pathway-related genes IGF2BP1 and IGF2BP3.

Method: We analysed here the association between T2D (and related traits) and rs4402960 and rs1470579 in IGF2BP2, and rs46522 and rs6949019 (marking IGF2BP1 and IGF2BP3 respectively) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (N approximately 2500 aged 65-96 years). We undertook a retrospective analysis of the deviations from the multiplicative model in previous studies and the present study.

Results: We replicated an association between rs4402960 and T2D status, and reported significant associations with anthropometric traits, fasting insulin, HOMA-IR and HOMA-%B. These associations were also observed for rs1470579, but not for the SNPs marking IGF2BP1 and IGF2BP3.

Conclusions: The lower fasting insulin levels and the impaired beta-cell function associated with IGF2BP2 SNPs are independent of obesity phenotypes. The action of these SNPs on T2D may result from an effect on beta-cell function. This could lead to lower insulin levels, the association with anthropometric traits being secondary. We discuss possible mechanisms of action relating IGF2BP2 with T2D traits. The occurrence of null alleles, the inclusion of T2D patients in analyses of metabolic syndrome risk traits and the genetic model, are possible factors accounting for non-replications of IGF2BP2 associations with T2D.

Figures

Figure 1
Figure 1
Graphical summary of the significant associations found under the recessive model for quantitative traits related to T2D when T2D patients are not considered in the analysis. The bars represent the mean values observed for each genotype for rs4402960 [a), b) and c)] and for rs1470579 [d), e) and f)]. The standard error of the mean is also shown for each case.
Figure 2
Figure 2
Graphical summary of the significant associations found under the recessive model for quantitative traits related to T2D when T2D patients are not considered in the analysis. The bars represent the mean values observed for each genotype for rs46522 [a), b) and c)] and for rs6949019 [d), e) and f)]. The standard error of the mean is also shown for each case.
Figure 3
Figure 3
Schematic representation of the relationships between IGF2BP2 genotype, insulin levels, obesity indices and T2D.

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