Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury

Barcelos, Gustavo Rafael Mazzaron; Grotto, Denise; Marco, Kátia Cristina de; Valentini, Juliana; Lengert, André van Helvoort; Oliveira, Andréia Ávila Soares de; Garcia, Solange Cristina; Braga, Gilberto Úbida Leite; Engström, Karin; Cólus, Ilce Mara de Syllos; Broberg, Karin; Barbosa, Fernando

doi:10.1016/j.scitotenv.2013.06.029

Cited by 59 publications

(54 citation statements)

References 36 publications

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“…Moreover, it is important to note that our population was not in Hardy-Weinberg equilibrium (HWE) for the allele frequencies of these genetic variants, which does not allow extrapolating data to other populations. One explanation for the HWE disequilibrium could be related to the heterogeneity ethnic in the Brazilian population, since is composed of Africans, Europeans, and indigenous ancestries (Barcelos et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers

Martins

Barcelos

Ferreira

et al. 2015

Journal of Toxicology and Environmental Health, Part A

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Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb.

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Section: Discussionmentioning

confidence: 99%

Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers

Martins

Barcelos

Ferreira

et al. 2015

Journal of Toxicology and Environmental Health, Part A

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“…Furthermore, it has recently been demonstrated that polymorphisms in glutathione-related genes modify Hg concentrations and antioxidant status in human subjects environmentally exposed to Hg [165]. …”

Section: Discussionmentioning

confidence: 99%

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

Kern

Haley

Geier

et al. 2013

IJERPH

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Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules.

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“…The GCLC SNP (Single Nucleotide Polymorphism) rs1555903 also showed a highly significant ( p = 0.007) main effect on mercury retention in the umbilical cord in a UK birth cohort (Julvez et al, 2013). Mutations in glutathione S-transferase mu 1 ( GSTM1 ) and GCLM also seem to affect the retention of methylmercury from fish and seafood (Barcelos et al, 2013). …”

mentioning

confidence: 99%

Genetic susceptibility to methylmercury developmental neurotoxicity matters

Júlvez

Grandjean

2013

Front. Genet.

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Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury

Cited by 59 publications

References 36 publications

Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers

Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

Genetic susceptibility to methylmercury developmental neurotoxicity matters

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