Genetic susceptibility to decompression sickness: molecular mechanisms, genomic advances, and precision prevention strategies

Abstract

Decompression sickness (DCS) is a multisystem disorder caused by rapid environmental pressure reduction, which causes the dissolved gas in the body to come out as bubbles, and subsequent multi-organ injury. A notable feature is great individual variation in sensitivity. Under identical pressure exposure conditions, some individuals develop severe DCS while others remain unaffected, indicating that host genetic background may play an important modulatory role in DCS. Recently, using selectively bred DCS‑resistant rat lines along with multi‑omics platforms such as genomics, transcriptomics, miRNomics and metabolomics, the molecular underpinnings of the susceptibility have started to emerge. Polymorphisms in innate‑immunity genes like MYD88 and NFKB1, variants in transthyretin (TTR), miRNA regulatory networks, and typical intestinal metabolic profiles are proposed as candidate elements for a multi-layered susceptibility architecture, although most current evidence comes from animal studies and needs to be validated in humans. In parallel, candidate biomarkers such as plasma gelsolin (pGSN), peripheral‑blood tau, and circulating extracellular vesicles offer potential tools for individual risk quantification. This review gathers recent progress, critically appraises the strength and independence of the underlying evidence, proposes a four‑layer susceptibility framework integrating genetic, molecular/epigenetic, metabolic/microbial, and physiological factors, contrasts this framework with classical bubble‑centered models, and discusses research gaps and translational priorities.