A Signature of Circulating MicroRNAs Predicts the Susceptibility of Acute Mountain Sickness

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. 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. 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, < 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, < 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. 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.