Genes related to IGF2 and related IGF binding proteins are associated with longitudinal trends in body-mass index

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 389-405-Signaling Originating from Membrane Receptors
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-392
Ram Prakash Narayanan*1, Bo Fu2, Antony Payton2, Rachelle P Donn2, Adrian H Heald1, William ER Ollier3 and J Martin Gibson1
1The University of Manchester, Salford, United Kingdom, 2The University of Manchester, Manchester, United Kingdom, 3Centre for Integrated Genomic Medical Research, Manchester, United Kingdom
High IGF-II has been associated with longitudinal weight loss in type 2 diabetes. We have studied associations of genes coding for IGF-II and for binding proteins that have preferential IGF-II affinity (IGFBP2, IGFBP5 and IGFBP6) in 991 Caucasian type 2 diabetes subjects from Salford, UK.
Fifteen IGF2, four IGFBP2, eight IGFBP5 and one IGFBP6 SNPs were successfully genotyped using a Sequenom platform. Longitudinal body-mass index data for the years 2002 to 2009 was obtained from integrated primary care and hospital electronic medical records. Mixed effects regression models were used to study SNPs as predictors of longitudinal body-mass index and the analyses were adjusted for age, gender and prescription of common diabetes medications that could affect weight (metformin, sulphonylureas, thiazolidinediones and insulin).
IGF2 rs12417332 and IGFBP5 rs4674107 was associated with weight gain, while IGFBP2 rs7603372, IGFBP2 rs9341105, IGFBP5 rs741384 and IGFBP5 rs7426116 were associated with longitudinal weight loss. All the significantly associated proteins were included in a stepwise regression model along with age, gender and the earlier medications as covariates. This identified three independent SNP associations– IGFBP2 rs9341105 (β = -0.12, 95% CI -0.20 to -0.04, p=0.001), IGFBP5 rs741384 (β= 0.12, 95% CI 0.06 to 0.18, p<0.001) and IGF2 rs12417332 (β= -0.12, 95% CI -0.22 to -0.023, p=0.016) remained.
IGF-II has been previously reported to have longitudinal associations with weight change, and the binding proteins IGFBP-2 and IGFBP-5 can potentially modify IGF bioavailability. This study suggests that SNPs within IGF2, IGFBP2 and IGFBP5 contribute to longitudinal weight trends in diabetes populations.

Nothing to Disclose: RPN, BF, AP, RPD, AHH, WEO, JMG

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