Genetic polymorphisms are associated with exposure biomarkers for metals and persistent organic pollutants among Inuit from the Inuvialuit Settlement Region, Canada

Background: Inuit are exposed to some of the highest levels of contaminants world wide. Studies suggest that several genes that mediate the metabolism of these contaminants are polymorphic. We hypothesize that single nucleotide polymorphisms (SNPs) in such genes may underline differences in biomarker concentrations and/or modify exposure-biomarker associations. Methods: Members from the Inuvialuit Settlement Region (Canada) were recruited. Blood concentrations of mercury (Hg), cadmium (Cd), lead (Pb), dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyl (PCB-153) were measured. SNPs from pathways such as glutathione, metallothionein, oxidative stress, and xenobiotic transport were genotyped in 281 participants, and data from 112 SNPs were included in the analyses. Surveys were administered to obtain information on demographics, and key sources of Hg (diet) and Cd (smoking) exposure. ANOVA and linear regressions were used for data analyses. Results: Geometric mean concentrations of metals were 4.6 mu g/L for Hg, 1.3 mu g/L for Cd, and 32.2 mu g/L for Pb. Concentrations of organic pollutants were 2.0 mu g/L for DDE and 0.6 mu g/L for PCB-153. Biomarker levels for Hg, Cd, Pb, DDE, and PCB-153 differed (p < 0.05) by genotype for 4, 3, 4, 3, and 3 SNPs, respectively. Inmultivariable analyses (for Pb, DDE, PCB-153) adjusting age, sex and body mass index (BMI), only 2 associations (one for Pb and one for DDE) remained significant. In multivariable analyses accounting for sources of Hg or Cd exposure, 24 SNPs (9 for Hg, 15 for Cd with 4 overlapping) had significant (p < 0.05) main effects on biomarker levels and/or modified exposure-biomarker associations. Conclusion: The findings suggest that polymorphisms in key environmentally responsive genes can influence biomarker levels and/or modify exposure-biomarker associations for contaminants of concern to Arctic populations. Consideration of such gene-environment results may help improve the ability to conduct exposure (and ultimately risk) assessments of country foods and Inuit health. (C) 2018 Elsevier B.V. All rights reserved.