Polymorphisms of genes related to metabolism of lead (Pb) are associated with the metal body burden and with biomarkers of oxidative stress

Individual susceptibility to the toxic effects induced by exposure to lead (Pb) may be affected by several variables, such as environmental factors, as well as intrinsic variations among the individuals, which are hypothetically associated to genetic differences in enzymes metabolizing the metal. Aim of the present study was to evaluate the effects of polymorphisms of glutathione (GSH)-genes related to the antioxidant status and Pb metabolism (GCLC, rs17883901 and GCLM, rs41303970) on Pb levels in blood (B-Pb) and plasma (P-Pb), as well as Pb-related effects on activity of glutathione-peroxidase (GPX) and on GSH concentrations. A cross-sectional study with 236 adults (men, > 18 years old) was carried out with workers from automotive battery factories, Brazil. B-Pb and P-Pb were determined by ICP-MS; blood GPX and GSH were determined by spectrophotometry and qPCR TaqMan assays were used for genotyping. A questionnaire was applied in order to collect socio-demographic, lifestyle and time of exposure. The mean B-Pb level was 211 +/- 118 mu g/L and P-Pb was 6.05 +/- 7.13 mu g/L. GCLM are associated with changes of B-Pb and P-Pb; individuals who carry at least one polymorphic allele for GCLM gene had lower metal levels in the blood and plasma (beta = -1.5; p = 0.0080; beta = -0.12 and p = 0.050). In addition, individuals carrying at least one polymorphic allele for the GCLC gene had higher concentrations of GSH than the non-polymorphic ones, as a function of B-Pb (beta = 0.072; p = 0.029). Significant associations were also observed with GCLC polymorphism on GSH concentrations (as a function of P-Pb), that is, polymorphic individuals tended to have higher concentrations of GSH than non-polymorphic ones (beta = 0.072; p = 0.030), while those individuals who are polymorphic for GCLM had higher activities of GPX, compared to the non-variant genotype (beta = 0.19; p = 0.028). Taken together, our data indicate that polymorphisms related to Pb toxicokinetics modify the metal body burden and Pb-related antioxidant effects. (AU)