title: 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.affiliation: Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine of USC, Los Angeles, California, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
authors.forename: Anny H
authors.initials: AH
authors.lastname: Xiang
authors.forename: Enrique
authors.initials: E
authors.lastname: Trigo
authors.forename: Jaana
authors.initials: J
authors.lastname: Hartiala
authors.forename: Jean M
authors.initials: JM
authors.lastname: Lawrence
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue; D050154:Adiposity / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D016640:Diabetes, Gestational / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000208:ethnology / Q000235:genetics*; D008297:Male; D017058:Mexican Americans / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C498779:IGF2BP2 protein, human; D016601:RNA-Binding Proteins