Glutathione peroxidase 3 is a potential biomarker for konzo
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.
Authors
- Victor Fourcassié (ORCID: https://orcid.org/0009-0003-7232-5314)
- Ljubica Caldovic (ORCID: https://orcid.org/0000-0002-9140-5585)
- D’Andre Spencer (ORCID: https://orcid.org/0000-0002-0145-9193)
- Matthew S. Bramble (ORCID: https://orcid.org/0000-0003-1216-7134)
- Florence Roux‐Dalvai (ORCID: https://orcid.org/0000-0002-9961-8964)
- Michel Lupamba Kasendue
- Marshall Summar
- Désiré Tshala-Katumbay (ORCID: https://orcid.org/0000-0003-0096-9471)
- Neerja Vashist (ORCID: https://orcid.org/0000-0002-1887-270X)
- Yun Zhou (ORCID: https://orcid.org/0009-0002-7411-3094)
- Rafael Vincent M. Manalo (ORCID: https://orcid.org/0000-0001-5763-1637)
- David R. McIlwain (ORCID: https://orcid.org/0000-0002-2537-0273)
- Michael J. Boivin (ORCID: https://orcid.org/0000-0002-0097-1777)
- Arnaud Droit (ORCID: https://orcid.org/0000-0001-7922-790X)
- Gary Cunningham
- Dieudonné Mumba Ngoyi (ORCID: https://orcid.org/0000-0002-5886-2004)
- Vincent Kambale-Mastaki
- Hilaire Musasa Hanshi-Hatuhu
- Aliyah Mohammed
- Éric Vilain
- Guy Makila Mabe Bumoko
Institutions
- Children's National (US)
- University of Nevada, Reno (US)
- University of California, Los Angeles (US)
- Oregon Health & Science University (US)
- George Washington University (US)
- University of California, Irvine (US)
- University of Kinshasa (CD)
- National Institute of Biomedical Research (CD)
- Université Laval (CA)
- University of the Philippines Manila (PH)
- Michigan State University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-06
- DOI
- https://doi.org/10.1038/s41467-024-52136-5
- Citations
- 3
- Primary Topic
- Cassava research and cyanide
- Type
- article
- Field-Weighted Citation Impact
- 1.80
Funders
- National Institutes of Health
- Fogarty International Center
- National Institute of Environmental Health Sciences