Location: Children's Nutrition Research CenterTitle: Genetic variants in IRS2 may contribute to obesity and diabetes familial risk in Hispanic children) Author
Submitted to: Obesity
Publication Type: Abstract only
Publication Acceptance Date: 6/15/2010
Publication Date: 11/1/2010
Citation: Butte, N.F., Cole, S.A., Haack, K., Comuzzie, A.G., Trevino, L., Muzny, D.M., Wheeler, D.A., Gibbs, R.A. 2010. Genetic variants in IRS2 may contribute to obesity and diabetes familial risk in Hispanic children [abstract]. Obesity. 18 (2):S190. Interpretive Summary:
Technical Abstract: IRS2 is a key regulator of glucose homeostasis and an obesity candidate gene, however, its role in children’s susceptibility to obesity and diabetes risk is unknown. Our specific aim was to identify genetic variants explaining a statistically significant quantitative trait locus on chromosome 13q for fasting serum glucose in Hispanic children enrolled in the VIVA LA FAMILIA Study. Exonic and intronic segments, and 5’ and 3’ flanking regions of IRS2 were sequenced in 934 Hispanic children. Bidirectional sequencing was performed using 373OXL DNA Sequencers. The resulting sequences were analyzed using SNPdetector and SNPs were confirmed manually using Sequencher. Measured genotype analysis tested associations between SNPs and phenotypes. A total of 146 SNPs were identified with minor allele frequencies ranging from 0.001 to 0.46. Of the 146 SNPs, 27 are described in public databases. Forty-two of the 73 coding SNPs result in nonsynonymous amino acid substitutions relative to the consensus sequence; 35 SNPs were detected in the promoter, 36 in the 3’UTR, and 2 in 5’UTR. Measured genotype analysis revealed 9 novel potentially functional SNPs associated with obesity and diabetes phenotypes in the coding and promoter regions. One synononymous SNP remained significantly associated with IGF1, after correction for multiple testing. Resequencing of IRS2 supports a functional role for rare IRS2 variants in the regulation of body weight and glucose homeostasis in Hispanic children.