Two novel microRNAs and their association with absolute blood pressure parameters in an urban South African community

Abstract

MicroRNAs are important in development of disease, and description of novel microRNAs adds to the pool of microRNAs that can be targeted for diagnostic and therapeutic purposes in disease. Herein, we aimed to describe novel microRNAs in a normotensive and hypertensive African population and relate their expression to blood pressure parameters and hypertension status. Previous work using next-generation sequencing showed differential expression of two novel microRNAs in the blood of normotensives and hypertensives. Herein, we have investigated these novel microRNAs by quantitative reverse transcription polymerase chain reaction in a cohort of 881 participants in this study. The relationship between the novel microRNAs and systolic and diastolic blood pressure as well as mean arterial pressure was also investigated. Age and sex-adjusted Spearman’s correlations were used to assess the relationship between microRNAs and cardiovascular risk profile variables whilst multivariable logistic regression models were used to assess the association of microRNAs with screen-detected and known hypertension. The novel microRNAs (miR-novel-chr1_36178 and miR-novel-chr15_18383) were significantly dysregulated by hypertension status. The expression of miR-novel-chr1_36178 differed according to sex, correlated with mean arterial pressure and systolic and diastolic blood pressure at higher levels of expression and was associated with screen-detected hypertension. The association of miR-novel-chr1_36178 expression with mean arterial pressure and systolic and diastolic blood pressure, as well as its dysregulation according to hypertension status suggests its possible utility as a biomarker target for hypertension diagnosis and/or therapeutics. Furthermore, its association with screen detected hypertension and dose-response relationship with blood pressure suggests it may be used to identify and monitor individuals at risk of hypertension.

Summary of Known Genetic and Epigenetic Modification Contributed to Hypertension

“…Using a microarray, Li et al [ 106 ] demonstrated that out of the total miRNAs detected in the experiment, 46 miRNAs were found to be profoundly expressed in hypertensive patients suggesting the miRNA contribution on the pathogenesis of hypertension [ 106 ]. Furthermore, dysregulation of miR-126-3p, 182-5p, and 30a-5p expression is evident to be the culprit of hypertension progression in the South African population meanwhile dysregulation of two novel miRNAs, miR-novel-chr1_36178 and miR-novel-chr15_18383, was significantly correlated with the SBP and DBP of the same population [ 104 , 107 ]. In addition, an elevation of the circulated miR-505 plasma level is found among spontaneously hypertensive rats and angiotensin II-infused mice related to endothelial dysfunction and inflammation [ 105 ].…”