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

Willian Robert Gomes; Paula Pícoli Devóz; Bruno Limonti Cano Luiz; Denise Grotto; Bruno Lemos Batista; Fernando Barbosa Jr; Gustavo Rafael Mazzaron Barcelos

doi:10.1016/j.mrgentox.2018.05.016

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

Mutat Res Genet Toxicol Environ Mutagen. 2018 Dec;836(Pt B):42-46. doi: 10.1016/j.mrgentox.2018.05.016. Epub 2018 May 25.

Authors

Willian Robert Gomes¹, Paula Pícoli Devóz¹, Bruno Limonti Cano Luiz¹, Denise Grotto², Bruno Lemos Batista³, Fernando Barbosa Jr¹, Gustavo Rafael Mazzaron Barcelos⁴

Affiliations

¹ Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, CEP 14040-903, Ribeirão Preto, Brazil.
² University of Sorocaba, Rodovia Raposo Tavares, km 92.5, CEP 18023-000 Sorocaba, SP, Brazil.
³ Center of Natural and Human Sciences, Federal University of ABC, Avenida dos Estados, 5001, CEP 09210-580, Santo André, Brazil.
⁴ Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Avenida Ana Costa, 95, Vila Matias, CEP 11.060-001, Santos, SP, Brazil. Electronic address: gustavo.barcelos@unifesp.br.

PMID: 30442344
DOI: 10.1016/j.mrgentox.2018.05.016

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 μg/L and P-Pb was 6.05 ± 7.13 μg/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 (β = -1.5; p = 0.0080; β = -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 (β = 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 (β = 0.072; p = 0.030), while those individuals who are polymorphic for GCLM had higher activities of GPX, compared to the non-variant genotype (β = 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.

Keywords: Glutathione; Lead; Metabolism; Oxidative stress; Polymorphisms; Toxicity.

MeSH terms

Adolescent
Adult
Aged
Biomarkers / analysis*
Body Burden
Brazil
Cross-Sectional Studies
Environmental Exposure / adverse effects*
Genotype
Glutamate-Cysteine Ligase / genetics*
Humans
Lead / adverse effects
Lead / analysis
Lead / metabolism*
Male
Middle Aged
Occupational Exposure / adverse effects*
Oxidative Stress
Polymorphism, Genetic*
Young Adult

Substances

Biomarkers
Lead
GCLC protein, human
GCLM protein, human
Glutamate-Cysteine Ligase