Project: Genetic and epigenetics of metals and nutritional factors

The individual genetic background makes us more or less susceptible to metals in the environment. Variation in the DNA sequence of 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. We have also identified genetic variation influencing the metabolism and toxicity of mercury and manganese and the metabolism of selenium. Moreover, factors that regulate gene expression, so-called epigenetic factors, have been identified as targets for metal toxicity and can explain long-term toxic effects. Evidence is rapidly growing for epigenetic effects of 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.

Financing

  • National Institute of Health
  • Swedish Research Council
  • Swedish Research Council Formas
  • Erik Philip Sörensons stiftelse
  • Karolinska Institutet

Selected publications

Vahter M, Broberg K, Harari F. Placental and Cord Blood Telomere Length in Relation to Maternal Nutritional Status. Journal of Nutrition 2020 Jul 17:nxaa198. doi: 10.1093/jn/nxaa198.

Broberg K, Taj T, Guazzetti S, Peli M, Cagna G, Pineda D, Placidi D, Wright RO, Smith DR, Lucchini RG, Wahlberg K. Manganese transporter genetics and sex modify the association between environmental manganese exposure and neurobehavioral outcomes in children. Environment International 2019:130:104908.

Herlin M, Broberg K, Malin Igra A, Li H, Harari F, Vahter M. Telomere length in mother-newborn pairs in relation to exposure to multiple toxic metals. BMC Medicine 2019,17(1):77.

Xu Y, Wahlberg K, Love TM, Watson GE, Yeates AJ, Mulhern MS, McSorley EM, Strain JJ, Davidson PW, Shamlaye CF, Rand MD, Myers GJ, van Wijngaarden E, Broberg K. Associations of blood mercury and fatty acid concentrations with blood mitochondrial DNA copy number in the Seychelles Child Development Nutrition Study. Environment International 2019;17;124:278-283.

Wahlberg KE, Guazzetti S, Pineda D, Larsson SC, Fedrighi C, Cagna G, Zoni S, Placidi D, Wright RO, Smith DR, Lucchini RG, Broberg K. Polymorphisms in Manganese Transporters SLC30A10 and SLC39A8 Are Associated With Children's Neurodevelopment by Influencing Manganese Homeostasis. Frontiers in Genetics 2018;9:664.

Gliga AR, Engström K, Kippler M, Skröder H, Ahmed S, Vahter M, Raqib R, Broberg K. Prenatal arsenic exposure is associated with increased plasma IGFBP3 concentrations in 9-year-old children partly via changes in DNA methylation. Archives in Toxicology 2018;92(8):2487-2500.