title: A Signature of Circulating microRNAs Predicts the Susceptibility of Acute Mountain Sickness.
abstract: Background:Acute mountain sickness (AMS) is a common disabling condition in individuals experiencing high altitudes, which may progress to life-threatening high altitude cerebral edema. Today, no established biomarkers are available for prediction the susceptibility of AMS. MicroRNAs emerge as promising sensitive and specific biomarkers for a variety of diseases. Thus, we sought to identify circulating microRNAs suitable for prediction the susceptible of AMS before exposure to high altitude.Methods:We enrolled 109 healthy man adults and collected blood samples before their exposure to high altitude. Then we took them to an elevation of 3648 m for 5 days. Circulating microRNAs expression was measured by microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). AMS was defined as Lake Louise score ≥3 and headache using Lake Louise Acute Mountain Sickness Scoring System.Results:A total of 31 microRNAs were differentially expressed between AMS and Non-AMS groups, 15 up-regulated and 16 down-regulated. Up-regulation of miR-369-3p, miR-449b-3p, miR-136-3p, and miR-4791 in patients with AMS compared with Non-AMS individuals were quantitatively confirmed using qRT-PCR (all,P< 0.001). With multiple logistic regression analysis, a unique signature encompassing miR-369-3p, miR-449b-3p, and miR-136-3p discriminate AMS from Non-AMS (area under the curve 0.986, 95%CI 0.970-1.000,P< 0.001, LR+: 14.21, LR-: 0.08). This signature yielded a 92.68% sensitivity and a 93.48% specificity for AMS vs. Non-AMS.Conclusion:The study here, for the first time, describes a signature of three circulating microRNAs as a robust biomarker to predict the susceptibility of AMS before exposure to high altitude.
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: Bing-Da
authors.initials: BD
authors.lastname: Sun
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: Er-Long
authors.initials: EL
authors.lastname: Zhang
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China; Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China; Key Laboratory of High Altitude Medicine, PLAChongqing, China.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Gao
keywords: acute mountain sickness; circulating microRNAs; prediction; signature