Project: Genetic and epigenetics of metals and nutritional factors

It has become increasingly clear that the individual genetic background influences the 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. Arsenic is one of the clearest examples, where genetic variation in AS3MT, the major arsenic-metabolizing gene, significantly contributes to the arsenic metabolism efficiency, and to a less extent to arsenic toxicity. Less is known about genetics for other toxic metals such as cadmium and mercury, or for essential elements such as manganese and selenium. Moreover, factors that regulate gene expression, so called epigenetic, have been identified as targets for metal toxicity. 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. In our studies of newborn, children and adults we investigate genes influencing metal metabolism and toxicity as well as epigenetic effects of metals.

Contact person

Karin Broberg, Professor

Financing

  • National Institute of Health
  • Erik Philip Sörensons stiftelse
  • Kungliga Fysiografiska Sällskapet
  • Karolinska Institutet

Selected publications

PUFA Status and Methylmercury Exposure Are Not Associated with Leukocyte Telomere Length in Mothers or Their Children in the Seychelles Child Development Study.
Yeates A, Thurston S, Li H, Mulhern M, McSorley E, Watson G, et al
J. Nutr. 2017 11;147(11):2018-2024

High levels of circulating folate concentrations are associated with DNA methylation of tumor suppressor and repair genes , , and in elderly Chileans.
Sanchez H, Hossain M, Lera L, Hirsch S, Albala C, Uauy R, et al
Clin Epigenetics 2017 ;9():74

CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment.
Llop S, Tran V, Ballester F, Barbone F, Sofianou-Katsoulis A, Sunyer J, et al
Environ Int 2017 08;105():34-42

Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women.
Engström K, Wojdacz T, Marabita F, Ewels P, Käller M, Vezzi F, et al
Arch. Toxicol. 2017 May;91(5):2067-2078

Exposure to Inorganic Arsenic Is Associated with Increased Mitochondrial DNA Copy Number and Longer Telomere Length in Peripheral Blood.
Ameer S, Xu Y, Engström K, Li H, Tallving P, Nermell B, et al
Front Cell Dev Biol 2016 ;4():87

Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function.
Wahlberg K, Kippler M, Alhamdow A, Rahman S, Smith D, Vahter M, et al
Toxicol. Sci. 2016 Feb;149(2):473-83

Selenium metabolism to the trimethylselenonium ion (TMSe) varies markedly because of polymorphisms in the indolethylamine N-methyltransferase gene.
Kuehnelt D, Engström K, Skröder H, Kokarnig S, Schlebusch C, Kippler M, et al
Am. J. Clin. Nutr. 2015 Dec;102(6):1406-15

Human adaptation to arsenic-rich environments.
Schlebusch C, Gattepaille L, Engström K, Vahter M, Jakobsson M, Broberg K
Mol. Biol. Evol. 2015 Jun;32(6):1544-55