Effects of genetic polymorphisms on antioxidant status and concentrations of the metals in the blood of riverside Amazonian communities co-exposed to Hg and Pb

• Study subjects are highly co-exposed to methylmercury and lead, via diet.
• Exposure to the metals leads to disturbances of antioxidant status.
• Polymorphisms related to kinetics of Hg and Pb may modulate metals bodyburden and toxicity.
• Genetic effects were seen also on parameters related to antioxidant status.
• ALAD polymorphism modifies Hg concentrations in blood, but not influences Pb levels.

There have been reports of genetic effects affecting the metabolism of Hg and Pb individually, and thus modulating their toxicities. However, there is still a knowledge gap with respect to how genetics may influence the toxicities of these toxic metals during a co-exposure scenario. This present study is therefore aimed at investigating the effects of polymorphisms in genes (GSTM1, GSTT1, GSTP1, GCLM, GCLC, GPx1, ALAD, VDR and MDR1) that have been implicated in Hg and Pb metabolisms affects the kinetics of these metals, as well as various blood antioxidant status parameters: MDA and GSH, and the activities of CAT, GPx and ALAD among populations that have been co-exposed to both Hg and Pb. Study subjects (207 men; 188 women) were from an Amazonian population in Brazil, exposed to Hg and Pb from diet. The blood levels of Hg and Pb were determined by ICP-MS while genotyping were performed by PCR assays. The median values of Hg and Pb in blood were 39.8 µg/L and 11.0 µg/dL, respectively. GSTM1, ALAD and VDR polymorphisms influenced Hg in blood (β=0.17; 0.37 and 0.17; respectively, p<0.050) while variations on GCLM, GSTT1 and MDR1 (TT) modulated the concentrations of Pb among the subjects (β=−0.14; 0.13 and −0.22; re–spectively, p<0.050). GSTT1 and GCLM polymorphisms also are associated to changes of MDA concentrations. Persons with null GSTM1 genotype had higher activity of the antioxidant enzyme CAT than carries of the allele. Individuals with deletion of both GSTM1 and GSTT1 had a decreased expression of GPx compared to those that expressed at least, one of the enzymes. ALAD 1/2 subjects had lower ALAD activity than individuals with the non-variant genotype. Our findings give further support that polymorphisms related to Hg and Pb metabolism may modulate Hg and Pb body burden and, consequently metals-induced toxicity.