Abstract
Circulating miRNAs isolated from dried blood spots (DBS) were found to be associated with high altitude sickness (HAS) patients in Tibet. HAS arises from two different diseases which are acute (AMS) and chronic (CMS) mountain sickness. Circulating miRNAs differences were found between AMS Han Chinese patients and normal Han controls and between CMS Tibetan Chinese patients and normal Tibetan controls. HAS arises from hypoxia which afflicts some high altitude inhabitants or visitors and not others. The difference results from each individual’s genetic makeup where hypoxia related genes have been shown to be a major contributor to these sicknesses. Several fold changes increases (up regulation) were found in the hypoxia associated miRNAs let-7f-5p, miR-9-5p, miR-19a-3p, miR-23a-3p, miR-98-5p, miR-125a-5p, miR-181b-5p, mir-202-3p, miR-372, miR-381-3p, miR-519d, miR-520d-3p, and miR-656 for both HAS groups compared to their controls. Other miRNAs (miR-19a-3p, 302c-3p and 875-3p) were found to be up regulated in one HAS group and down regulated in the other HAS group indicating the genetic differences between the two sickness groups.
Highlights
MicroRNAs are 18- to 25-nucleotides, non-coding RNA molecules that regulate the expression of many genes
We find that miRNAs can be obtained from dried blood spots (DBS) and that the miRNA data when compared between a normal group and a high altitude sickness (HAS) patient group revealed changes in miRNAs that regulate hypoxia genes associated with HAS
Hypoxia leads to an increase in the hypoxia-inducible factor (HIF) activity that induces the expression of genes which mediates the adaptive responses through glycolytic enzymes, hemeoxygenase, vascular endothelial growth factor (VEGF) and erythropoietin (EPO) [28, 42]
Summary
MicroRNAs (miRNAs) are 18- to 25-nucleotides, non-coding RNA molecules that regulate the expression of many genes. Since their discovery, miRNAs have been found to regate a variety of cellular processes including apoptosis, differentiation and cell proliferation [1]. Circulating miRNAs are found in all compartments of the blood, including plasma, platelets, erythrocytes and nucleated blood cells [2]. These circulating miRNAs are found to be remarkably stable in plasma even under harsh conditions as boiling, low or high pH, longterm storage at room temperature and in multiple freeze-thaw cycles [2,3]. The condition is generally self limiting; most symptoms disappear after two to three days, insomnia may persist [11]
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