Expression of Microrna in Whole Blood of Active Pulmonary Tuberculosis Patients With or Without Hiv Co-Infection at Selected Health Centres in Oromia Region, Ethiopia
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Date
2015-09-04
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Addis Ababa University
Abstract
Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) infections dysregulate the host immune response via interactions with multiple cells. However, the mechanism underlying the synergy between Mtb and HIV are not fully understood. Recently non-coding microRNAs (miRNAs), which are involved in many cellular processes by regulating the translation of coding mRNAs, have been suggested to be involved in the molecular pathogenesis of Mtb and HIV. But the expression profile of miRNAs in Mtb/HIV co-infection has barely been studied. In this study, we explored the differential expression of miRNAs in whole blood of patients with pulmonary tuberculosis (PTB) with or without HIV co-infection compared to uninfected healthy controls. The study included baseline samples from participants recruited from four health centres in Oromia Region, Ethiopia. The expression profile of miRNAs was measured using Affymetrix microarray. Using the significant analysis of microarray (SAM), we identified a total of 83 differentially expressed miRNAs comparing all the three groups (q=0). Hierarchical clustering analysis based on these miRNAs revealed clear separation among these groups. Compared with uninfected controls, the expression of 35 miRNAs was significantly altered in the PTB patients with HIV co-infection. There were only three miRNAs that distinguished PTB patients from uninfected controls. In contrast, a set of 77 miRNAs differentiated PTB patients from the PTB/HIV co-infected patients. Among these we found miR-150, miR-223, and family members of let-7, miR-27 and miR-26 that previously have been characterized as immune regulatory miRNAs during Mtb and HIV-1 infections. Overall, these results indicate that the expression of a large number of miRNAs are altered in PTB/HIV patients compared with the PTB cases without HIV infection, as well as the uninfected individuals, suggesting that HIV co-infection might have a profound impact on the dysregulation of miRNAs in whole blood of PTB patients. These findings provide, at least preliminary data, in support of further basic research and open new insights into the underlying mechanisms of miRNAs involvement in the pathogenesis of Mtb/HIV co-infection. Such studies may be used to develop biomarkers for the diagnostic purposes of TB/HIV co-infection.
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Keywords
Ethiopia, Mtb/Hiv Co-Infection, Microarray, Micrornas, Differential Expression, Hierarchical Clustering