Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans

Obesity (Silver Spring). 2009 Apr;17(4):729-36. doi: 10.1038/oby.2008.593. Epub 2009 Jan 15.


Genome-wide association studies showed variation in insulin-like growth factor-2 binding protein 2 (IGF2BP2) to be associated with type 2 diabetes mellitus (T2DM). We examined a 20-kb region of IGF2BP2 for association with T2DM-related quantitative traits in Mexican American families of a proband with gestational diabetes mellitus (GDM) from the BetaGene study. We genotyped 14 single-nucleotide polymorphisms (SNPs) in 717 individuals from 146 families phenotyped by oral glucose tolerance test (OGTT), intravenous glucose tolerance tests (IVGTTs) with minimal model analysis, and dual-energy X-ray absorptiometry scan for percent body fat. Three SNPs and one SNP combination that captured the majority of the variation in the region were tested for association with T2DM-related quantitative traits using a variance components framework. After correction for multiple testing, rs11705701 showed association with percent body fat (P(ACT) = 0.041) with body fat decreasing approximately 1.5-2% per copy of the A allele. We next tested whether the interaction between rs11705701 and body fat was associated with T2DM-relative quantitative traits. rs11705701 was significantly associated with insulin sensitivity (Bonferroni P = 0.028) and marginally associated with OGTT 2-h insulin (Bonferroni P = 0.066) and disposition index (DI) (Bonferroni P = 0.072). We conclude that rs11705701 in IGF2BP2 is associated with body fat and this effect on body fat influences insulin resistance which may contribute to T2DM risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adipose Tissue
  • Adiposity / ethnology
  • Adiposity / genetics*
  • Adult
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes, Gestational / ethnology
  • Diabetes, Gestational / genetics*
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance / ethnology
  • Insulin Resistance / genetics*
  • Male
  • Mexican Americans / ethnology
  • Mexican Americans / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Pregnancy
  • RNA-Binding Proteins / genetics*


  • IGF2BP2 protein, human
  • RNA-Binding Proteins