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Zhang et al. J Transl Genet Genom 2018;2:18                  Journal of Translational
               DOI: 10.20517/jtgg.2018.22                                  Genetics and Genomics




               Original Article                                                              Open Access


               Plasma microRNA profiles identify distinct clinical
               phenotypes in human asthmatics


               Simin Zhang , Zoe Laryea , Ronaldo Panganiban , Kristin Lambert , Diana Hsu , Faoud T. Ishmael 1,2
                                                                         1
                                                          1
                                                                                   1
                          1#
                                      1#
               1 Deparment of Medicine, The Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
               2 Mount Nittany Medical Center, State College, PA 16801, USA.
               # These authors contributed equally.
               Correspondence to: Dr. Faoud T. Ishmael, Department of Medicine, The Pennsylvania State University Milton S. Hershey Medical
               Center, Hershey, PA 17033, USA. E-mail: fishmael@pennstatehealth.psu.edu
               How to cite this article: Zhang S, Laryea Z, Panganiban R, Lambert K, Hsu D, Ishmael FT. Plasma microRNA profiles identify distinct
               clinical phenotypes in human asthmatics. J Transl Genet Genom 2018;2:18. https://doi.org/10.20517/jtgg.2018.22
               Received: 7 Jul 2018    First Decision: 28 Sep 2018    Revised: 15 Oct 2018   Accepted: 15 Oct 2018    Published: 7 Nov 2018

               Science Editor: Faoud Terrence Ishmael    Copy Editor: Cui Yu    Production Editor: Zhong-Yu Guo



               Abstract
               Aim: Asthma is a chronic inflammatory syndrome that is characterized by heterogeneous disease pathogeneses that
               produce distinct subtypes. There is a great need to develop biomarkers to distinguish these subtypes and help guide
               specific therapy and better predict outcomes, particularly in severe asthma where a number of targeted therapeutics are
               now available. We sought to determine whether expression of asthma-specific microRNAs (miRNAs) could distinguish
               phenotypic differences in a diverse cohort of asthmatic subjects that spanned a range of disease severity.

               Methods: RNA was isolated from peripheral blood from human subjects. Expression of 39 miRNAs was then screened.
               Sample cycle threshold values were normalized. Normally distributed data were analyzed and hierarchical cluster was
               performed.

               Results: Peripheral blood was obtained from 62 adults. We identified four clusters of asthmatics defined by 5 distinct
               miRNA expression patterns. Cluster 1 was associated with mild asthma, low inhaled corticosteroid use, and low eosinophil
               levels. Cluster 3 and 4 consisted primarily of severe asthmatics with poor asthma control, and Cluster 3 was specifically
               associated with high IgE, high blood eosinophil levels, and racial disparity (higher proportion of Black subjects). Cluster 2
               was comprised predominantly of mild-moderate asthmatics that had higher blood eosinophils than Cluster 1.

               Conclusion: These results indicate the miRNA expression profiling can be useful to identify distinct asthma phenotypes,
               and have potential to better understand disease pathogenesis and help guide therapy.

               Keywords: Asthma, allergic rhinitis, microRNA, biomarker, real-time PCR, predictive modeling


                           © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
                           International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
                sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
                as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
                and indicate if changes were made.


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