Abstract 20768: Racial Differences in Circulating miRNA and Metabolomic Profiles of Participants in the Morehouse and Emory Team Up to Eliminate Health Disparities Study
Introduction: The extracellular detection of miRNAs has sparked interest in their role as paracrine signals and biomarkers for cardiovascular disease (CVD). Metabolomics investigates the metabolic network and specific biochemical pathways. We hypothesized that an integrative analysis of circulating miRNA and metabolomic profiles has the potential to identify novel biomarkers and enable a systems biology approach to understanding disparities in CVD. Little is known about the impact of race on these profiles, which we examined here.
Methods: The META-Health Study was a cross-sectional study of risk factors for CVD in a group of self-reported black and white residents of Atlanta. Archived plasma samples from 52 black and 52 white participants were match by propensity scores based on CVD risk factors. High-resolution metabolomics profiling was performed on plasma, and levels of select miRNAs (miR-10b, -93, -181a, 182) were assessed by RT-qPCR of RNA extracted from microparticle (MP) fraction of plasma. Paired LIMMA analysis was used to identify differentially expressed metabolites, and Partial Least Squares method in mixOmics R package was used for miRNA-metabolome network analysis at different correlation thresholds.
Results: Blacks had higher MP counts compared to whites (p<0.005). Levels of miR-93, -181a and -182 were lower in blacks (p = 0.0016, p = 0.012, p = 0.04, respectively). Twenty-six metabolites were found to be differentially expressed between blacks and whites at FDR<0.2 and 99 metabolites were found to be differentially expressed at a raw p<0.05. A miRNA-metabolome wide association study of the 99 metabolites and miR-181a and -182 showed 20 that were strongly associated with these miRNAs at a correlation of 0.30. These metabolites were enriched in metabolic pathways pathways (p<0.05) implicated in CVD, including linoleate, leukotriene, glutathione, and biopterin metabolism.
Conclusions: These data demonstrate racial differences in molecular profiles and provide the basis for studies that examine the impact of CVD on these profiles. An integrative analysis of circulating metabolites and miRNAs can identify biomarkers for metabolic phenotype and provide insight into genetic and environmental influences on CVD disparities.
Author Disclosures: A. James: None. K. Uppal: None. S. Thomas: None. K. Rooney: None. Y. Ko: None. H.A. Taylor: None. A.A. Quyyumi: None. D.P. Jones: None. C.D. Searles: None.
- © 2016 by American Heart Association, Inc.