Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives
| Autor: | Jason E. Gosschalk, E. R. Ali, L. A. Okitundu, J. P. Banea, Matthew S. Bramble, D. L. Yandju, Michael J. Boivin, D. Larry, F.A. Rwatambuga, Eric Vilain, D. Mumba Ngoyi, Desire Tshala-Katumbay, Morris Kim, Shawn K. Westaway |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Models Molecular medicine.medical_specialty Manihot Sulfurtransferase Serum Albumin Human Toxicology Polymorphism Single Nucleotide Article Foodborne Diseases 03 medical and health sciences 0404 agricultural biotechnology Internal medicine medicine Humans Cognitive Dysfunction Amino Acid Sequence Motor Neuron Disease Protein carbamoylation Child 030304 developmental biology Konzo 0303 health sciences Protein Carbamylation business.industry Neurodegeneration Albumin Motor control 04 agricultural and veterinary sciences General Medicine medicine.disease 040401 food science Thiosulfate Sulfurtransferase Endocrinology Case-Control Studies Sulfurtransferases Toxicity Democratic Republic of the Congo Female business Thiosulfate sulfurtransferase Food Science |
| Zdroj: | Food Chem Toxicol |
| ISSN: | 1873-6351 |
| Popis: | A case-control design determined whether konzo, an upper motoneuron disease linked to food (cassava) toxicity was associated with protein carbamoylation and genetic variations. Exon sequences of thiosulfate sulfurtransferase (TST) or mercaptopyruvate sulfurtransferase (MPST), plasma cyanide detoxification rates, and 2D-LC-MS/MS albumin carbamoylation were assessed in 40 children [21 konzo-affected and 19 putatively healthy controls, mean (SD) age: 9.2 (3.0) years] subjected to cognition and motor testing using the Kaufman Assessment Battery and the Bruininks/Oseretsky Test, respectively. Konzo was significantly associated with higher levels of carbamoylated peptides 206–219 (LDELRDEGKASSAK, pep1) after adjusting for age, gender, albumin concentrations and BUN [regression coefficient: 0.03 (95%CI:0.02 – 0.05), p = 0.01]. Levels of pep1 negatively correlated with performance scores at all modalities of motor proficiency (r = 0.38 to 0.61; all p < 0.01) or sequential processing (memory)(r = − 0.59, p = 0.00) and overall cognitive performance ( r = − 0.48, p = 0.00) but positively with time needed for cyanide detoxification in plasma (r = 0.33, p = 0.04). Rare potentially damaging TST p.Arg206Cys (rs61742280) and MPST p.His317Tyr (rs1038542246) heterozygous variants were identified but with no impact on subject phenotypes. Protein carbamoylation appears to be a reliable marker for cassava related neurodegeneration. |
| Databáze: | OpenAIRE |
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