
School of Medicine Publications and Presentations
Document Type
Article
Publication Date
4-1-2015
Abstract
Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤- 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤- 10-4) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase1B (ADH1B) that was significantly enriched (P < 10-60) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data.We observed significant inverse correlations with waist circumference (2.8 × 10-9), BMI (5.4 × 10-6), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.
Recommended Citation
Winnier, D. A., Fourcaudot, M., Norton, L., Abdul-Ghani, M. A., Hu, S. L., Farook, V. S., ... & Jenkinson, C. P. (2015). Transcriptomic identification of ADH1B as a novel candidate gene for obesity and insulin resistance in human adipose tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES). PloS one, 10(4), e0119941. https://doi.org/10.1371/journal.pone.0119941
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
PLoS ONE
DOI
10.1371/journal.pone.0119941
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication