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

Abstract

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.

• Authors: Xia Li, Hooman Allayee, Anny H Xiang, Enrique Trigo, Jaana Hartiala, Jean M Lawrence, Thomas A Buchanan, Richard M Watanabe
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 17 Issue 4 Pg. 729-36 (Apr 2009) ISSN: 1930-7381 [Print] United States
• PMID: 19148120 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• IGF2BP2 protein, human
• RNA-Binding Proteins

Topics

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