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)

Deidre A. Winnier, Marcel Fourcaudot, Luke Norton, Muhammad A. Abdul-Ghani, Shirley L. Hu, Vidya S. Farook, Dawn K. Coletta, Satish Kumar, Sobha Puppala, Geetha Chittoor, Thomas D. Dyer, Rector Arya, Melanie Carless, Donna M. Lehman, Joanne E. Curran, Douglas T. Cromack, Devjit Tripathy, John Blangero, Ravindranath Duggirala, Harald H H GöringRalph A. DeFronzo, Christopher P. Jenkinson

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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.

Original languageEnglish (US)
Article number119941
JournalPloS one
Volume10
Issue number4
DOIs
StatePublished - Apr 1 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Winnier, D. A., Fourcaudot, M., Norton, L., Abdul-Ghani, M. A., Hu, S. L., Farook, V. S., Coletta, D. K., Kumar, S., Puppala, S., Chittoor, G., Dyer, T. D., Arya, R., Carless, M., Lehman, D. M., Curran, J. E., Cromack, D. T., Tripathy, D., Blangero, J., Duggirala, R., ... 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), [119941]. https://doi.org/10.1371/journal.pone.0119941