Abstract 20498: Transcriptome-Wide Analysis Reveals Differential Expression of Histone Genes Associated With Dysregulation of Immune System in High Versus Low Stress African Americans

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Background: African Americans experience higher rates of premature of morbidity and mortality from stress-related cardiovascular diseases compared to European Americans. Stress-related alterations in physiological processes has been hypothesized to partially explain these racial differences. However, little is known about the molecular mechanism underlying stress response in African Americans. Here, we investigated the association of perceived stress with transcriptome-wide gene expression in African Americans using next generation RNA sequencing.

Methods and Results: We used whole blood samples from 63 African Americans (33 with high stress and 30 with low stress) obtained from the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) study. Perceived stress was assessed using a 14-item version of perceived stress scale. We identified a total of 59 differentially expressed genes (DEGs), with 48 up-regulated and 11 downregulated genes in high stress compared to low stress African Americans after adjusting for confounding covariates and correction for false discovery rate (FDR < 5%). The results revealed upregulation of several genes related to histone clusters, immunoglobulin, and cell cycle. Furthermore, the functional annotation of the DEGs showed that the histone genes were highly enriched in GO terms of nucleosome assembly and regulation of gene expression epigenetic, and pathways of systemic lupus erythematous at an FDR < 5%.

Conclusions: Our findings suggest that epigenetic mechanisms may play potential role in regulation of gene expression in response to psychosocial stress. Future research is warranted to elucidate the functional consequences of epigenetic mechanisms in dysregulation of immune system and development of autoimmune diseases in African Americans.

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