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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.

SUBMITTER: Li X

PROVIDER: S-EPMC4357482 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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

Li Xia X Allayee Hooman H Xiang Anny H AH Trigo Enrique E Hartiala Jaana J Lawrence Jean M JM Buchanan Thomas A TA Watanabe Richard M RM

Obesity (Silver Spring, Md.) 20090115 4

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 (O ...[more]

PMID: 19148120

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Project description:ContextA central/visceral fat distribution and excess free fatty acid (FFA) availability are associated with dyslipidemia and insulin resistance. However, these two characteristics often coexist, making it difficult to detect the independent contributions of each. Whether FFA suppression is more closely linked to metabolic abnormalities is not clear.ObjectiveThe aim of the study was to examine the relationship between FFA suppression, body fat distribution, and fitness as contributors toward insulin resistance and hypertriglyceridemia.DesignWe measured systemic palmitate turnover using an iv infusion of [9,10-(3)H]palmitate; upper body sc adipose tissue (UBSQ) and visceral adipose tissue (VAT) with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan; fitness with a graded exercise treadmill test; and insulin sensitivity with both the iv glucose tolerance test (IVGTT) (SI(IVGTT)) and mixed meal tolerance test (SI(Meal)).SettingThe study was conducted at a General Clinical Research Center.ParticipantsBaseline data were obtained from 140 elderly adults (age, 60-88 yr; 83 males) and 60 young adults (age, 18-31 yr; 31 males) who participated in a previously published trial assessing the effects of 2-yr supplementation of dehydroepiandrosterone or testosterone on body composition, glucose metabolism, and bone density.InterventionsThere were no interventions.Main outcome measuresWe measured fasting plasma triglyceride (TG) concentrations, SI(IVGTT), and SI(Meal).ResultsUsing multivariate regression analysis, the strongest combined predictors of TG concentrations were VAT, postmeal nadir FFA concentrations, sex, and age. The best predictors of SI(IVGTT) were IVGTT nadir palmitate concentration, VAT, UBSQ fat, fitness, and age, whereas the best predictors of SI(Meal) were meal nadir palmitate concentration, UBSQ fat, fitness, and sex.ConclusionsFFA suppression is associated with both fasting TG concentrations and insulin sensitivity, independent of measures of adiposity.

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

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

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