Paul A Tambyah1, Chai S Ching2, Sugunavathi Sepramaniam2, Jaminah M Ali1, Arunmozhiarasi Armugam2, Kandiah Jeyaseelan3. 1. Department of Medicine, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore. 2. Department of Biochemistry, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore. 3. Department of Biochemistry, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia bchjeya@nus.edu.sg.
Abstract
BACKGROUND: Dengue is the most common arboviral illness worldwide. While most infected patients recover, a proportion of them develop severe complications or fatality. Nevertheless, the pathophysiological mechanisms which distinguish the disease severity and associated complications are not clearly understood. We studied blood profiles of dengue patients in order to identify microRNAs that could play a role in these pathophysiological mechanisms. METHODS: Blood samples from 26 dengue-infected patients were collected within 0-14 days of infection. Together with samples obtained from six healthy individuals, microRNA profiles were generated to identify significantly altered microRNAs upon dengue infection. Profiles of patients with influenza were also used to determine the disease specificity of these altered microRNAs. Their discriminative power to distinguish dengue from influenza was then tested statistically. RESULTS: Several significantly altered microRNAs were identified in patients with dengue. Twelve microRNAs were specifically altered upon acute dengue whereas 14 microRNAs exhibited similar expression between dengue and influenza. Seventeen microRNAs which could potentially distinguish dengue-related complications were also identified. Expression of miR-24-1-5p, miR-512-5p and miR-4640-3p distinguished mild dengue from those exhibiting liver complications whereas miR-383 was significantly upregulated in mild dengue compared to those diagnosed as severe dengue with fluid accumulation. CONCLUSIONS: We identified two panels of microRNAs - one specific for dengue and the other common to dengue and influenza. We also report on the differentially expressed microRNAs in patients with mild versus severe dengue, which could be the basis for the complications seen in them.
BACKGROUND: Dengue is the most common arboviral illness worldwide. While most infectedpatients recover, a proportion of them develop severe complications or fatality. Nevertheless, the pathophysiological mechanisms which distinguish the disease severity and associated complications are not clearly understood. We studied blood profiles of dengue patients in order to identify microRNAs that could play a role in these pathophysiological mechanisms. METHODS: Blood samples from 26 dengue-infectedpatients were collected within 0-14 days of infection. Together with samples obtained from six healthy individuals, microRNA profiles were generated to identify significantly altered microRNAs upon dengue infection. Profiles of patients with influenza were also used to determine the disease specificity of these altered microRNAs. Their discriminative power to distinguish dengue from influenza was then tested statistically. RESULTS: Several significantly altered microRNAs were identified in patients with dengue. Twelve microRNAs were specifically altered upon acute dengue whereas 14 microRNAs exhibited similar expression between dengue and influenza. Seventeen microRNAs which could potentially distinguish dengue-related complications were also identified. Expression of miR-24-1-5p, miR-512-5p and miR-4640-3p distinguished mild dengue from those exhibiting liver complications whereas miR-383 was significantly upregulated in mild dengue compared to those diagnosed as severe dengue with fluid accumulation. CONCLUSIONS: We identified two panels of microRNAs - one specific for dengue and the other common to dengue and influenza. We also report on the differentially expressed microRNAs in patients with mild versus severe dengue, which could be the basis for the complications seen in them.
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