Abstract 435: Differential mRNA and MicroRNA Expression is Influenced by Race in Hypertensive and Non-hypertensive Women

Abstract

Systemic arterial hypertension occurs more frequently among African Americans (AA) than any other population sub-group, has earlier onset, and more frequently results in end-organ complications. In addition, AA women have the highest incidence and hospitalization rates for hypertension. Previous data suggests that gene expression patterns may increase individual susceptibility to selected chronic diseases. Therefore, we hypothesized that differential gene expression may influence the disproportionate incidence and prevalence of hypertension among AAs. Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) from AA or White, normotensive or hypertensive females identified thousands of mRNAs differentially expressed by race or presence of hypertension. Since microRNAs (miRNAs) are well-known post-transcriptional regulators of mRNA expression levels, and recent data indicates that miRNAs play an important role in the etiology of cardiovascular disease, we wanted to examine whether changes in miRNA abundance underlie changes in gene expression with hypertension. To test this, we profiled global miRNA expression in the same cohort. Analysis of microarray expression changes using Ingenuity Pathway Analysis identified mRNA-miRNA regulatory networks in hypertension-related pathways, i.e. the renin-angiotensin system, nitric oxide signaling, and actin cytoskeletal signaling pathways, which differ by race and hypertension status. mRNA and miRNA gene expression changes were validated using RT-qPCR in an expanded cohort and gene functionality and miRNA target validation was investigated in vitro using primary human umbilical vein cells. We have identified several miRNAs, including miRs 20a-5p, 103a-2-5p, 30c-5p, 4763-5p, 4709-3p and 4717-3p, which are significantly (P<0.05) and differentially expressed by race and/or presence of hypertension. Together, these findings identify several pathways and miRNA gene candidates whose expression differ with race and may contribute to hypertension-related health disparities and could potentially serve as biomarkers for hypertension or as targets for therapeutic modalities.