Predictive value of microRNAs and cytokines in the development of type 2 diabetes mellitus and hypertension in a South African mixed ancestry population

Abstract

The increasing burden of cardiometabolic diseases (CMDs) like Type 2 diabetes mellitus (T2DM) and hypertension in South Africa is a matter of significant concern, particularly among individuals of mixed ancestry, and the diagnosis of these conditions with currently adopted methodologies remains sub-optimal. The pathophysiology of these two CMDs is strongly influenced by inflammatory pathways mediated by cytokines, which regulate chronic inflammation in CMDs. These cytokines are in turn regulated by short, non-coding RNAs such as microRNAs (miRNAs). Altered expression of miRNAs and cytokines has been associated with CMD development, and as such may be leveraged as early diagnostic markers for CMDs to supplement existing methods. As such, using RNA isolation and quantitative reverse transcription polymerase chain reaction methodologies, this study explored the relationship between circulatory extracellular vesicle (EV)-derived miR-92a and miR-29a and cytokine profiles in a mixed ancestry population living with T2DM and hypertension, to illuminate our understanding of the mechanisms underlying these CMDs. The investigations did not show a significant difference in the expression of miR-92a-3p and miR-29a in various glycaemic and hypertension groups (p ≥ 0.234), although the expression of miR-92a-3p increased with increasing blood pressure and thus was notably higher in hypertensive than in normotensives, whilst the highest expression of miR-29a-3p was seen in normotensives, and lowest in the pre-hypertensive group. TNF-α did not indicate any significant difference in expression levels between different glycaemic or hypertensive states (p ≥ 0.344). However, TNF-α levels significantly correlated with monocyte levels in the pre-hypertensive group and AST levels in normoglycaemic individuals. Overall, the expression patterns of both miRNAs in this study did not support their use as biomarkers for the diagnosis of either dysglycaemia or hypertension. The expression of both miRNAs correlated with monocytes and AST (r ≥0.649, p ≤ 0.044). Overall, the expression patterns of both miRNAs and TNF-α in this study did not support their use as biomarkers for the diagnosis of either dysglycaemia or hypertension, despite uncovering relations between these miRNAs and cytokines with other clinical parameters that can be further investigated.