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

Author(s)

Gomes, Willian Robert ; Devoz, Paula Picoli ; Cano Luiz, Bruno Limonti ; Grotto, Denise ; Batista, Bruno Lemos ; Barbosa, Fernando, Jr. ; Mazzaron Barcelos, Gustavo Rafael

• Document type: Journal article
• Source: MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS; v. 836, p. 5-pg., 2018-12-01.

Abstract

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)

• FAPESP's process: 15/07277-3 - Evaluation of lead exposure on the methylation pattern of promoter regions of genes associated to the metal metabolism, in workers of automotive battery industries
• Grantee: Paula Pícoli Devóz
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/01157-6 - Influence of glutamyl-cysteine ligase (catalytic subunit, GCLC, and modifier, GLCM) gene polymorphisms evaluation on lead concentrations in workers exposed to metal
• Grantee: Bruno Limonti Cano Luiz
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/24981-3 - Combining omics tools for predicting multivariate models in populations exposed to toxic metals
• Grantee: Gustavo Rafael Mazzaron Barcelos
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 13/06033-8 - Combining omics tools for predicting multivariate models in populations exposed to toxic metals
• Grantee: Gustavo Rafael Mazzaron Barcelos
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/04786-4 - Evaluation of lead-induced oxidative stress exposure in workers of automotive battery plants
• Grantee: Willian Robert Gomes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation