Connection between genes, response to environmental chemicals

"We believe that the interplay between an individual's genetics and the environment is a key to answering questions like, 'Why do some drugs work well for some people but not others?' or 'Why does pollution affect people differently?'" says David Reif, associate professor of biology at NC State and corresponding author of the study. "We wanted to address two related problems: Of all the tens of thousands of chemicals to which we are exposed, do some elicit differential sensitivity? And are there genetic factors that explain differential sensitivity?"

The team from NC State and Oregon State analyzed high throughput screening data to find patterns of interindividual variability in response to chemical exposure: in other words, they looked for chemicals that elicited differing responses from individuals. Eventually, they narrowed thousands of potential chemicals to one: abamectin. Abamectin is a commonly used antiparasitic that showed differential susceptibility in zebrafish.

In a series of assays, the researchers looked at abamectin's effect on zebrafish during early developmental stages. They then compared the genomes of affected (abnormally developed) versus unaffected (normally developed, or "healthy") zebrafish and discovered an association with the gene Sox7, which controls how the body forms in vertebrate animals. Zebrafish affected by abamectin had a slightly different variant of the sox7 gene than the unaffected individuals. Additionally, affected zebrafish expressed a lower level of their sox7 gene in targeted follow-up experiments.

"This study is a starting point to confirm that individuals may react differently to chemicals in the environment based upon genetic profile," Reif says. "Our high throughput screening approach allows us to quickly sort through the 'exposome' of chemicals to which we are exposed and look for relationships between genetics and environmental exposure, rather than be limited to preselected candidate exposures. The work has implications for precision medicine, disease prevention and understanding how risk may differ across communities."

The research appears in Environmental Health Perspectives and was supported by the National Institute of Environmental Health Sciences (grants U01 ES027294, P42 ES005948, P30 ES025128, P42 ES016465, 5T32 ES007329); the Environmental Protection Agency (STAR Grants 835168 and 835796); and the National Science Foundation Graduate Research Fellowship Grant No. DGE-1252376. The team included former graduate student Michelle Balik-Meisner (first author) and Elizabeth Scholl from NC State; and Lisa Truong, Jane La Du and Robert Tanguay from Oregon State University.