Identifying Effects of UCP3G403A Polymorphism Metabolomic Profiles
Project Number: 5306-51530-019-78
Specific Cooperative Agreement
Start Date: Jan 27, 2013
End Date: Jul 31, 2013
Collaborative efforts associated with the National Institutes of Health (NIH) funded R01: Identification of Biomarkers of Beta-oxidation, has generated three large metabolomics data sets which have independently provided novel insights into the phenotypic consequences of diabetes. However, to date, the implications of the UCP3 G403A polymorphism also represented in this experiment have not been explored. In the current project, the existing datasets will be merged and evaluated using a suite of multivariate statistical approaches to explore and report the metabolic consequences of this functional polymorphism in the UCP3 gene to enhance our understanding of the endogenous role of this enzyme involved in mitochondrial uncoupling. A secondary objective of this analysis will be to statistically associate unknowns identified in the global metabolomics platform with knowns from the acyl-carnitine and lipid mediator platforms, providing an alternative means of functionally linking unknowns to known biological functions. Results will be prepared in a publication-ready manuscript.
Three existing datasets (1 - the global metabolomic profiles; 2 – the comprehensive acyl-carnitine profile; 3 - the plasma fatty acid and lipid mediator profile) derived from the analysis of BMI matched subjects with and without diabetes and with or without the UCP3G403A polymorphism will be merged and analyzed using a combination of multivariate statistics including hierarchical cluster analysis, partial least squares analysis, partial least squares discriminant analysis and regression analyses. Analyses will primarily be accomplished by implementation using the R-Statistical Computing Environment and limited network analysis in cytoscape.