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Genetic variant in the IGF2BP2 gene may interact with fetal malnutrition to affect glucose metabolism.

van Hoek M, Langendonk JG, de Rooij SR, Sijbrands EJ, Roseboom TJ - Diabetes (2009)

Bottom Line: Previous studies showed that these effects may be modulated by genetic variation.Genome-wide association studies discovered and replicated a number of type 2 diabetes-associated genes.This may provide a clue that modulation of the consequences of fetal environment depends on an individual's genetic background.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

ABSTRACT

Objective: Fetal malnutrition may predispose to type 2 diabetes through gene programming and developmental changes. Previous studies showed that these effects may be modulated by genetic variation. Genome-wide association studies discovered and replicated a number of type 2 diabetes-associated genes. We investigated the effects of such well-studied polymorphisms and their interactions with fetal malnutrition on type 2 diabetes risk and related phenotypes in the Dutch Famine Birth Cohort.

Research design and methods: The rs7754840 (CDKAL1), rs10811661 (CDKN2AB), rs1111875 (HHEX), rs4402960 (IGF2BP2), rs5219 (KCNJ11), rs13266634 (SLC30A8), and rs7903146 (TCF7L2) polymorphisms were genotyped in 772 participants of the Dutch Famine Birth Cohort Study (n = 328 exposed, n = 444 unexposed). Logistic and linear regression models served to analyze their interactions with prenatal exposure to famine on type 2 diabetes, impaired glucose tolerance (IGT), and area under the curves (AUCs) for glucose and insulin during oral glucose tolerance testing (OGTT).

Results: In the total population, the TCF7L2 and IGF2BP2 variants most strongly associated with increased risk for type 2 diabetes/IGT and increased AUC for glucose, while the CDKAL1 polymorphism associated with decreased AUC for insulin. The IGF2BP2 polymorphism showed an interaction with prenatal exposure to famine on AUC for glucose (beta = -9.2 [95% CI -16.2 to -2.1], P = 0.009).

Conclusions: The IGF2BP2 variant showed a nominal interaction with exposure to famine in utero, decreasing OGTT AUCs for glucose. This may provide a clue that modulation of the consequences of fetal environment depends on an individual's genetic background.

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Related in: MedlinePlus

The effect of the IGF2BP2 genotypes on AUC glucose according to prenatal exposure to famine. Number of subjects shown inside of each bar, SEs of the mean shown on top of each bar. , GG; ■, GT; □, TT.
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Figure 1: The effect of the IGF2BP2 genotypes on AUC glucose according to prenatal exposure to famine. Number of subjects shown inside of each bar, SEs of the mean shown on top of each bar. , GG; ■, GT; □, TT.

Mentions: Table 3 shows the interactions between genetic variants and exposure to famine in utero. The IGF2BP2 showed a significant interaction on AUC glucose (β interaction −9.2 [−16.2 to −2.1], P = 0.009).Figure 1 shows the effects of the IGF2BP2 polymorphism on AUC for glucose in exposed and unexposed subjects. After Bonferroni correction for 21 tests, this was no longer significant. None of the polymorphisms showed a significant interaction with birth weight (data not shown). Additional adjustments in multivariate models did not change the results.


Genetic variant in the IGF2BP2 gene may interact with fetal malnutrition to affect glucose metabolism.

van Hoek M, Langendonk JG, de Rooij SR, Sijbrands EJ, Roseboom TJ - Diabetes (2009)

The effect of the IGF2BP2 genotypes on AUC glucose according to prenatal exposure to famine. Number of subjects shown inside of each bar, SEs of the mean shown on top of each bar. , GG; ■, GT; □, TT.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2682678&req=5

Figure 1: The effect of the IGF2BP2 genotypes on AUC glucose according to prenatal exposure to famine. Number of subjects shown inside of each bar, SEs of the mean shown on top of each bar. , GG; ■, GT; □, TT.
Mentions: Table 3 shows the interactions between genetic variants and exposure to famine in utero. The IGF2BP2 showed a significant interaction on AUC glucose (β interaction −9.2 [−16.2 to −2.1], P = 0.009).Figure 1 shows the effects of the IGF2BP2 polymorphism on AUC for glucose in exposed and unexposed subjects. After Bonferroni correction for 21 tests, this was no longer significant. None of the polymorphisms showed a significant interaction with birth weight (data not shown). Additional adjustments in multivariate models did not change the results.

Bottom Line: Previous studies showed that these effects may be modulated by genetic variation.Genome-wide association studies discovered and replicated a number of type 2 diabetes-associated genes.This may provide a clue that modulation of the consequences of fetal environment depends on an individual's genetic background.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

ABSTRACT

Objective: Fetal malnutrition may predispose to type 2 diabetes through gene programming and developmental changes. Previous studies showed that these effects may be modulated by genetic variation. Genome-wide association studies discovered and replicated a number of type 2 diabetes-associated genes. We investigated the effects of such well-studied polymorphisms and their interactions with fetal malnutrition on type 2 diabetes risk and related phenotypes in the Dutch Famine Birth Cohort.

Research design and methods: The rs7754840 (CDKAL1), rs10811661 (CDKN2AB), rs1111875 (HHEX), rs4402960 (IGF2BP2), rs5219 (KCNJ11), rs13266634 (SLC30A8), and rs7903146 (TCF7L2) polymorphisms were genotyped in 772 participants of the Dutch Famine Birth Cohort Study (n = 328 exposed, n = 444 unexposed). Logistic and linear regression models served to analyze their interactions with prenatal exposure to famine on type 2 diabetes, impaired glucose tolerance (IGT), and area under the curves (AUCs) for glucose and insulin during oral glucose tolerance testing (OGTT).

Results: In the total population, the TCF7L2 and IGF2BP2 variants most strongly associated with increased risk for type 2 diabetes/IGT and increased AUC for glucose, while the CDKAL1 polymorphism associated with decreased AUC for insulin. The IGF2BP2 polymorphism showed an interaction with prenatal exposure to famine on AUC for glucose (beta = -9.2 [95% CI -16.2 to -2.1], P = 0.009).

Conclusions: The IGF2BP2 variant showed a nominal interaction with exposure to famine in utero, decreasing OGTT AUCs for glucose. This may provide a clue that modulation of the consequences of fetal environment depends on an individual's genetic background.

Show MeSH
Related in: MedlinePlus