VARIATION IN INSULIN-LIKE GROWTH FACTOR-2 BINDING PROTEIN 2 INTERACTS WITH ADIPOSITY TO ALTER INSULIN SENSITIVITY IN MEXICAN AMERICANS by Xia Li ________________________________________________________________________ A Thesis Presented to the FALCULTY OF THE KECK SCHOOL OF MEDICINE UNIVERSITY OF SOUTHERN CAILFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (APPLIED BIOSTATISTICS AND EPIDEMIOLOGY) December 2008
Copyright 2008 Xia Li
GWA studies have shown that variation in IGF2BP2 is associated with T2DM. We examined a 20 kb region of IGF2BP2 for association with T2DM-related quantitative traits in Mexican American families from the BetaGene study. We genotyped 14 SNPs in 783 individuals from 146 families phenotyped by OGTT, IVGTT, and DEXA scan for percent body fat. Three SNPs and one SNP combination were tested for association with T2DM-related quantitative traits using a variance components framework. rs11705701 showed association with adiposity (P_ACT=0.041), whereby body fat decreased ~1.5-2% per copy of the A allele. We next tested whether rs11705701 interacted with body fat to affect T2DM-related quantitative traits. The joint effect of rs11705701 and its interaction with percent body fat was significantly associated with S_I (Bonferroni p=0.028). We conclude that rs11705701 is associated with body fat and this effect on body fat influences insulin resistance which may contribute to T2DM.