Gene-environment interactions and metal toxicity
Broberg, Karin LU
and Pawlas, Natalia
(2021)
p.349-368
- Abstract
Humans are exposed to various metals through many different routes and each person’s genetic background contributes to their susceptibility to metal toxicity. In addition, recent evidence points to a role for the genetics of the human microbiome in metal uptake and toxicity. DNA sequence variation in genes that regulate metal toxicokinetics and toxicodynamics influences metal accumulation and retention in the body, as well as the associated toxic effects. The emerging picture shows that genetic susceptibility is unlikely to be conferred by a single gene specific for each metal, but is rather a polygenic trait combining small- and large-effect genes. The presence of genetic variants in the human leukocyte antigen system and the risk of... (More)
Humans are exposed to various metals through many different routes and each person’s genetic background contributes to their susceptibility to metal toxicity. In addition, recent evidence points to a role for the genetics of the human microbiome in metal uptake and toxicity. DNA sequence variation in genes that regulate metal toxicokinetics and toxicodynamics influences metal accumulation and retention in the body, as well as the associated toxic effects. The emerging picture shows that genetic susceptibility is unlikely to be conferred by a single gene specific for each metal, but is rather a polygenic trait combining small- and large-effect genes. The presence of genetic variants in the human leukocyte antigen system and the risk of beryllium-related pulmonary disease were one of the first examples of a gene-environment interaction. Genes important for susceptibility have been identified for arsenic (AS3MT), lead (ALAD), and manganese (SLC30A10). Moreover, emerging evidence points to effects of metals such as arsenic, cadmium, and lead on the epigenetic landscape, and epigenetic factors have been identified as targets for metal toxicity. Indeed, epigenetic effects may explain the noted association between metal exposure early in life and the later manifestation of toxic effects, as well as metal carcinogenicity. This chapter summarizes the current state of knowledge concerning such gene-environment interactions for metal toxicity.
(Less)
- author
- Broberg, Karin
LU
and Pawlas, Natalia
- organization
- publishing date
- 2021
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- keywords
- Copy number variation, DNA methylation, Effect modification, Epigenetic, Histone modification, microRNA, Mixed exposure, Omics, Polymorphisms, SNP, Susceptibility
- host publication
- Handbook on the Toxicology of Metals : Volume I: General Considerations - Volume I: General Considerations
- pages
- 20 pages
- publisher
- ScienceDirect, Elsevier
- external identifiers
-
- scopus:85134757747
- scopus:85129612929
- ISBN
- 9780128232934
- 9780128232927
- DOI
- 10.1016/B978-0-12-823292-7.00010-3
- language
- English
- LU publication?
- yes
- id
- df416e56-d87b-4782-8d16-59486185a18f
- date added to LUP
- 2022-07-05 14:33:31
- date last changed
- 2024-06-25 21:30:08
@inbook{df416e56-d87b-4782-8d16-59486185a18f,
abstract = {{<p>Humans are exposed to various metals through many different routes and each person’s genetic background contributes to their susceptibility to metal toxicity. In addition, recent evidence points to a role for the genetics of the human microbiome in metal uptake and toxicity. DNA sequence variation in genes that regulate metal toxicokinetics and toxicodynamics influences metal accumulation and retention in the body, as well as the associated toxic effects. The emerging picture shows that genetic susceptibility is unlikely to be conferred by a single gene specific for each metal, but is rather a polygenic trait combining small- and large-effect genes. The presence of genetic variants in the human leukocyte antigen system and the risk of beryllium-related pulmonary disease were one of the first examples of a gene-environment interaction. Genes important for susceptibility have been identified for arsenic (AS3MT), lead (ALAD), and manganese (SLC30A10). Moreover, emerging evidence points to effects of metals such as arsenic, cadmium, and lead on the epigenetic landscape, and epigenetic factors have been identified as targets for metal toxicity. Indeed, epigenetic effects may explain the noted association between metal exposure early in life and the later manifestation of toxic effects, as well as metal carcinogenicity. This chapter summarizes the current state of knowledge concerning such gene-environment interactions for metal toxicity.</p>}},
author = {{Broberg, Karin and Pawlas, Natalia}},
booktitle = {{Handbook on the Toxicology of Metals : Volume I: General Considerations}},
isbn = {{9780128232934}},
keywords = {{Copy number variation; DNA methylation; Effect modification; Epigenetic; Histone modification; microRNA; Mixed exposure; Omics; Polymorphisms; SNP; Susceptibility}},
language = {{eng}},
pages = {{349--368}},
publisher = {{ScienceDirect, Elsevier}},
title = {{Gene-environment interactions and metal toxicity}},
url = {{http://dx.doi.org/10.1016/B978-0-12-823292-7.00010-3}},
doi = {{10.1016/B978-0-12-823292-7.00010-3}},
year = {{2021}},
}