Association of PKLR gene copy number, expression levels and enzyme activity with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin in Vietnam.

Vuong, NB ; Quang, HV ; et al.

In: Chemosphere, Jg. 329 (2023-07-01), S. 138677

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2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is the most toxic congener of dioxin and has serious long-term effects on the environment and human health. Pyruvate Kinase L/R (PKLR) gene expression levels and gene variants are associated with pyruvate kinase enzyme deficiency, which has been identified as the cause of several diseases linked to dioxin exposure. In this study, we estimated PKLR gene copy number and gene expression levels using real-time quantitative PCR (RT-qPCR) assays, genotyped PKLR SNP rs3020781 by Sanger sequencing, and quantified plasma pyruvate kinase enzyme activity in 100 individuals exposed to Agent Orange/Dioxin near Bien Hoa and Da Nang airfields in Vietnam and 100 healthy controls. The means of PKLR copy numbers and PKLR gene expression levels were significantly higher, while pyruvate kinase enzyme activity was significantly decreased in Agent Orange/Dioxin-exposed individuals compared to healthy controls (P < 0.0001). Positive correlations of PKLR gene copy number and gene expression with 2,3,7,8-TCDD concentrations were observed (r = 0.2, P = 0.045 and r = 0.54, P < 0.0001, respectively). In contrast, pyruvate kinase enzyme activity was inversely correlated with 2,3,7,8-TCDD concentrations (r = -0.52, P < 0.0001). PKLR gene copy number and gene expression levels were also inversely correlated with pyruvate kinase enzyme activity. Additionally, PKLR SNP rs3020781 was found to be associated with 2,3,7,8-TCDD concentrations and PKLR gene expression. In conclusion, PKLR copy number, gene expression levels, and pyruvate kinase enzyme activity are associated with 2,3,7,8-TCDD exposure in individuals living in Agent Orange/Dioxin-contaminated areas.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Titel:	Association of PKLR gene copy number, expression levels and enzyme activity with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin in Vietnam.
Autor/in / Beteiligte Person:	Vuong, NB ; Quang, HV ; Linh Trang, BN ; Duong, DH ; Toan, NL ; Tong, HV
Link:	Zum Volltext
Zeitschrift:	Chemosphere, Jg. 329 (2023-07-01), S. 138677
Veröffentlichung:	Oxford : Elsevier Science Ltd ; <i>Original Publication</i>: Oxford, New York, : Pergamon Press., 2023
Medientyp:	academicJournal
ISSN:	1879-1298 (electronic)
DOI:	10.1016/j.chemosphere.2023.138677
Schlagwort:	Humans Agent Orange Vietnam Pyruvate Kinase genetics 2,4-Dichlorophenoxyacetic Acid analysis 2,4,5-Trichlorophenoxyacetic Acid analysis Gene Dosage Polychlorinated Dibenzodioxins analysis Dioxins toxicity Dioxins analysis
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Chemosphere] 2023 Jul; Vol. 329, pp. 138677. <i>Date of Electronic Publication: </i>2023 Apr 13. MeSH Terms: Polychlorinated Dibenzodioxins* / analysis ; Dioxins* / toxicity ; Dioxins* / analysis ; Humans ; Agent Orange ; Vietnam ; Pyruvate Kinase / genetics ; 2,4-Dichlorophenoxyacetic Acid / analysis ; 2,4,5-Trichlorophenoxyacetic Acid / analysis ; Gene Dosage Contributed Indexing: Keywords: 2,3,7,8-TCDD; Agent orange/dioxin; Gene copy number variation; PKLR gene; PKLR polymorphism; Pyruvate kinase Substance Nomenclature: 39277-47-9 (Agent Orange) ; 0 (Polychlorinated Dibenzodioxins) ; 0 (Dioxins) ; EC 2.7.1.40 (Pyruvate Kinase) ; 2577AQ9262 (2,4-Dichlorophenoxyacetic Acid) ; 9Q963S4YMX (2,4,5-Trichlorophenoxyacetic Acid) SCR Disease Name: Pyruvate Kinase Deficiency of Red Cells Entry Date(s): Date Created: 20230415 Date Completed: 20230502 Latest Revision: 20230502 Update Code: 20240514

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