Genetic Polymorphisms are Associated with Body Burden of Metals, Persistent Organic Pollutants (POPs) and Omega-3 Fatty Acids Levels among Inuit in the Canadian Arctic

Abstract

Introduction: Fish and marine mammals are dietary staples for Inuit residing in the Canadian Arctic. This diet is a source of both nutrients [docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)] and toxicants [mercury (Hg), dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyls (PCBs)]. Exposures to cadmium (Cd) and lead (Pb) and genetic variability in toxicant and nutrient metabolism further impact Inuit health. We hypothesize that single nucleotide polymorphisms (SNPs) underline inter-individual differences in biomarker concentrations of toxicants and omega-3 fatty acids. Methods: During the 2007-2008 International Polar Year Inuit Health Survey, 362 adults were recruited from the Inuvialuit Settlement Region (ISR) of Canada. Hg, Cd, and Pb were quantified in whole blood, DDE and PCB-153 in plasma, and DHA and EPA in red blood cells. Polymorphisms relevant to toxicant or lipid metabolism were genotyped in 280 participants with biomarker data. ANOVA and linear regressions were used for statistical analysis. Results: Biomarker levels for Hg, Cd, Pb, DDE, and PCB 153 varied by genotype for 11, 7, 9, 8, or 6 SNPs, respectively (p<0.05, ANOVA). DHA and EPA levels differed by genotype of 12 and 9 SNPs, respectively. Following Bonferroni correction, genotype-biomarker relationships remaining significant were: rs1056836 with Cd, rs1042838 with Cd and DDE, rs180040 and rs4671393 with DHA and EPA, and rs11644094 with DHA. When linear regression was used to assess the association between SNPs and Hg or Cd biomarker concentrations adjusting for reported sources of exposure, 16 and 24 SNPs had significant (p<0.05) main effects and/or gene-exposure source interactions for Hg and Cd. Conclusion: Polymorphisms can influence biomarker levels of toxicants as well as omega-3 fatty acids. Consideration of gene-environment relationships may improve the ability to assess the health risks and benefits of the Inuit diet.