Proteomics in Deaths by Drowning: Diagnostic Efficacy of Apolipoprotein A1 and α-1 Antitrypsin, Pilot Study

Abstract

Drowning is one of the leading causes of death worldwide. The pathophysiology of drowning is complex and, sometimes, interpretation of the circumstances of death in the autopsy becomes the main source of information in its diagnosis. New advances in medical research, such as proteomics, especially in forensic pathology, are still in the development. We proposed to investigate the application of Mass Spectrometry-based technologies, to identify differentially expressed proteins that may act as potential biomarkers in the postmortem diagnosis of drowning. We performed a pilot proteomic experiment with the inclusion of two drowned and two control forensic cases. After applying restrictive parameters, we identified apolipoprotein A1 (ApoA1) and α-1 antitrypsin as differentially expressed between the two diagnostic groups. A validation experiment, with the determination of both proteins in 25 forensic cases (16 drowned and 9 controls) was performed, and we corroborated ApoA1 higher values in the drowning group, whereas α-1 antitrypsin showed lower levels. After adjusting by confounder factors, both remained as predictive independent factors for diagnosis of drowning (p = 0.010 and p = 0.022, respectively). We constructed ROC curves for biomarkers’ levels attending at the origin of death and established an ApoA1 cut-off point of 100 mg/dL. Correct classification based on the diagnosis criteria was reached for 73.9% of the cases in a discriminant analysis. We propose apolipoprotein A1 (with our cutoff value for correct classification) and α-1 antitrypsin as valuable biomarkers of drowning. Our study, based on forensic cases, reveals our proteomic approach as a new complementary tool in the forensic diagnosis of drowning and, perhaps, in clinical future implications in drowned patients. However, this is a pilot approach, and future studies are necessary to consolidate our promising preliminary data.

Keywords

• proteomics
• drowning
• forensic diagnosis
• apolipoprotein A1
• α-1 antitrypsin