Gene-Environment Interactions for Metals

Research output: Chapter in Book/Report/Conference proceedingBook chapter

Abstract

It has become increasingly clear that the individual genetic background influences susceptibility to metal toxicity. Genetic variation in genes that regulate metal toxicokinetics and toxicodynamics influence the degree of metal accumulation and retention in the body, as well as toxic effects. Moreover, factors that regulate gene expression, so-called epigenetic factors, have been identified as targets for metal toxicity. This chapter addresses what is currently known about such gene-environment interactions. The picture that emerges for most metals is that the genetic influence is probably not attributed to a single gene for each metal; rather it is polygenic, with some genes having a stronger effect than others. The presence of variants of the human leukocyte antigen system and the risk of beryllium-related pulmonary disease was one of the first and maybe the strongest example of a gene-environment interaction. There are also clear gene-environment interactions for arsenic and lead. Evidence is rapidly growing for epigenetic effects of metals, e.g. for arsenic, cadmium, and lead, which may explain the association between metal exposure early in life and toxic effects later in life, as well as metal carcinogenicity.

Details

Authors
Organisations
External organisations
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Environmental Health and Occupational Health

Keywords

  • Copy number variation, DNA methylation, Effect modification, Epigenetic, Histone modification, MicroRNA, Polymorphisms SNP, Susceptibility
Original languageEnglish
Title of host publicationHandbook on the Toxicology of Metals
EditorsGunnar Nordberg, Bruce Fowler, Monica Nordberg
PublisherElsevier Inc.
Chapter12
Pages239-264
Volume1
Edition4th
ISBN (Electronic)9780123973399
ISBN (Print)9780444594532
Publication statusPublished - 2014 Oct 28
Publication categoryResearch
Peer-reviewedYes