Gene Expression in Decompression Sickness secondary to Underwater Compressed Gas Diving

Introduction: Gene expression analysis and biomarker discovery on decompression sickness (DCS) is a research niche. Previous research on rats with DCS has demonstrated significant differential gene and protein expression. DCS diagnosis may be challenging, particularly since it mimics other common medical presentations. Investigating gene expression in humans with DCS compared to closely-matched controls can shed light on susceptibility and biomarker profiles. Such information might benefit divers wishing to tailor their diving practices, and physicians involved in the management of divers and fitness for diving consultations. Moreover, this may lead to discovery of biomarkers to facilitate timely DCS diagnosis. Materials and Methods: Subjects diagnosed with DCS presenting within 8 hours of symptom onset were recruited. Controls were divers who surfaced symptom-free from ≥25 metres seawater maximum depth. Whole blood was sampled at presentation and at 40-44 hours after surfacing on PAXgene® Blood RNA Tubes (PreAnalytiX, Hombrechtikon, Switzerland). RNA extraction was performed using PAXgene Blood RNA kit (Qiagen, Venlo, Netherlands). Two-step quality control (QC) followed using spectrophotometry (Nanodrop) and bioanalyzer (Agilent 2100) for RIN (RNA Integrity Number). Transcriptome analysis by RNA-Seq and bioinformatic analysis to identify differentially expressed genes was carried out. Results: Paired blood samples were collected from nine cases and 17 controls. RNA-extraction was performed on seven random cases and six random controls. Following two-step QC, 13 case samples and 11 control samples met required criteria. QC confirmed RIN ≥8.1 in all samples and RNA concentrations of >20ng/μL in all but one. RNA-SEQ was run on 24 samples. Pathway analysis of differentially expressed genes between cases and controls identified statistically significant over-representation of cytokine-cytokine receptor interaction, the MAPK signaling pathway and the RAP1 signaling pathway. Conclusion: This area of research remains understudied, with data restricted mainly to animal studies. Future genome and proteome expression studies in human DCS are required.