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Racial differences in microRNA and gene expression in hypertensive women
Douglas F Dluzen1, Nicole Noren Hooten1, Yongqing Zhang2
1Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Insights
African American women experience higher rates of hypertension. This study found significant differences in gene and microRNA expression between African American and white hypertensive women, potentially explaining health disparities.
Area of Science:
- Genomics
- Cardiovascular Disease Research
- Health Disparities
Background:
- Systemic arterial hypertension is a major cause of cardiovascular morbidity and mortality.
- African Americans, particularly women, face disproportionately higher rates of hypertension incidence, prevalence, and severity.
- Differential gene expression is implicated in disease susceptibility and may contribute to health disparities.
Purpose of the Study:
- To investigate gene and microRNA expression differences in African American versus white women with and without hypertension.
- To identify novel mRNA-microRNA pairs associated with hypertension and race.
- To explore potential molecular mechanisms underlying hypertension health disparities.
Main Methods:
- Transcriptional profiling of peripheral blood mononuclear cells from African American and white, normotensive and hypertensive females.
- Global microRNA expression profiling.
- Validation of gene expression using RT-qPCR and microRNA target validation in endothelial cells.
Main Results:
- Thousands of mRNAs were differentially expressed by race and/or hypertension status.
- Significant gene expression differences were most prominent in African American hypertensive females.
- Novel differentially-expressed mRNA-microRNA pairs, including MCL1/miR-20a-5p and PLD1/miR-4717-3p, were identified.
Conclusions:
- Significant gene and microRNA expression differences exist between African American and white hypertensive females.
- Identified mRNA-microRNA pairs may play a role in hypertension-related pathways and contribute to health disparities.
- These molecular differences represent potential targets for future hypertension interventions.
Abstract:
Systemic arterial hypertension is an important cause of cardiovascular disease morbidity and mortality. African Americans are disproportionately affected by hypertension, in fact the incidence, prevalence, and severity of hypertension is highest among African American (AA) women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases and we hypothesized that this phenomena may affect health disparities in hypertension. Transcriptional profiling of peripheral blood mononuclear cells from AA or white, normotensive or hypertensive females identified thousands of mRNAs differentially-expressed by race and/or hypertension. Predominant gene expression differences were observed in AA hypertensive females compared to AA normotensives or white hypertensives. Since microRNAs play important roles in regulating gene expression, we profiled global microRNA expression and observed differentially-expressed microRNAs by race and/or hypertension. We identified novel mRNA-microRNA pairs potentially involved in hypertension-related pathways and differently-expressed, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, and PLD1/miR-4709-3p. We validated gene expression levels via RT-qPCR and microRNA target validation was performed in primary endothelial cells. Altogether, we identified significant gene expression differences between AA and white female hypertensives and pinpointed novel mRNA-microRNA pairs differentially-expressed by hypertension and race. These differences may contribute to the known disparities in hypertension and may be potential targets for intervention.
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