Glutathione peroxidase 3 is a potential biomarker for konzo

Matthew S. Bramble, Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA. mbramble@childrensnational.org.
Victor Fourcassié, Computational Biology Laboratory and The Proteomics Platform, CHU de Québec - Université Laval Research Center, Québec City, QC, Canada.
Neerja Vashist, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Florence Roux-Dalvai, Computational Biology Laboratory and The Proteomics Platform, CHU de Québec - Université Laval Research Center, Québec City, QC, Canada.
Yun Zhou, Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Guy Bumoko, Department of Neurology, Kinshasa University, Kinshasa, Democratic Republic of the Congo.
Michel Lupamba Kasendue, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo.
D'Andre Spencer, Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Hilaire Musasa Hanshi-Hatuhu, Department of Neurology, Kinshasa University, Kinshasa, Democratic Republic of the Congo.
Vincent Kambale-Mastaki, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo.
Rafael Vincent Manalo, Biological Models Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines, Manila, Ermita, Manila, Philippines.
Aliyah Mohammed, Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
David R. McIlwain, Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
Gary Cunningham, Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Marshall Summar, Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Michael J. Boivin, Departments of Psychiatry and Neurology & Ophthalmology, Michigan State University, East Lansing, MI, USA.
Ljubica Caldovic, Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Eric Vilain, Institute for Clinical and Translational Science, University of California, Irvine, CA, USA.
Dieudonne Mumba-Ngoyi, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo.
Desire Tshala-Katumbay, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo. tshalad@OHSU.edu.
Arnaud Droit, Computational Biology Laboratory and The Proteomics Platform, CHU de Québec - Université Laval Research Center, Québec City, QC, Canada. arnaud.droit@crchudequebec.ulaval.ca.

Document Type

Journal Article

Publication Date

9-6-2024

Journal

Nature communications

Volume

15

Issue

1

DOI

10.1038/s41467-024-52136-5

Abstract

Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the world's poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.

Department

Genomics and Precision Medicine

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