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


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.
van Hoek
Mandy
M
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Langendonk
Janneke G
JG
de Rooij
Susanne R
SR
Sijbrands
Eric J G
EJ
Roseboom
Tessa J
TJ
D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000196:embryology / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D020869:Gene Expression Profiling; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D044342:Malnutrition / Q000196:embryology / Q000235:genetics*; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000235:genetics*; D013217:Starvation / Q000196:embryology / Q000235:genetics*; D014857:Warfare
D001786:Blood Glucose; C498779:IGF2BP2 protein, human; D007328:Insulin; D016601:RNA-Binding Proteins