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Variation in IGF2BP2 Interacts With Adiposity to Alter Insulin Sensitivity in Mexican Americans
Author(s) -
Li Xia,
Allayee Hooman,
Xiang Anny H.,
Trigo Enrique,
Hartiala Jaana,
Lawrence Jean M.,
Buchanan Thomas A.,
Watanabe Richard M.
Publication year - 2009
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2008.593
Subject(s) - medicine , insulin resistance , single nucleotide polymorphism , endocrinology , bonferroni correction , type 2 diabetes , type 2 diabetes mellitus , insulin , snp , body mass index , gestational diabetes , biology , diabetes mellitus , genotype , genetics , pregnancy , gestation , statistics , mathematics , gene
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 ∼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.