Influence of<i>VDR</i>and<i>HFE</i>polymorphisms on blood lead levels of occupationally exposed workers

Mani, Monica Shirley; Puranik, Amitha; Kabekkodu, Shama Prasada; Joshi, Manjunath B.; Dsouza, Herman Sunil

doi:10.1177/0960327120975451

Cited by 1 publication

(1 citation statement)

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“…Although no direct effects may be related to the HFE gene and oxidative DNA damage, it is important to highlight that several underlying interactions may be related to HFE and Pb body burden, which may impact the toxicity of the metal. One hypothesis for this finding is that high levels of Pb are related to the polymorphic alleles for the HFE gene; in this context, it is notable that since such HFE SNPs directly impact Pb concentrations in the body, one possible explanation for our findings is that high Pb concentrations are directly associated with increased oxidative stress, inducing damage to various macromolecules, such as lipids, proteins, and mostly DNA (for review see Nersesyan et al [ 51 ] and Lopes et al [ 6 ]); it is well known that 8-OHdG is one of the most abundant oxidized metabolites related to DNA-damage induced by oxidative stress [ 43 ].…”

Section: Discussionmentioning

confidence: 83%

Association between Polymorphisms of Hemochromatosis (HFE), Blood Lead (Pb) Levels, and DNA Oxidative Damage in Battery Workers

Gomes

Devóz

Rocha

et al. 2023

IJERPH

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Occupational exposure to lead (Pb) continues to be a serious public health concern and may pose an elevated risk of genetic oxidative damage. In Brazil, car battery manufacturing and recycling factories represent a great source of Pb contamination, and there are no guidelines on how to properly protect workers from exposure or to dispose the process wastes. Previous studies have shown that Pb body burden is associated with genetic polymorphisms, which consequently may influence the toxicity of the metal. The aim of this study was to assess the impact of Pb exposure on DNA oxidative damage, as well as the modulation of hemochromatosis (HFE) polymorphisms on Pb body burden, and the toxicity of Pb, through the analysis of 8-hydroxy-2′-deoxyguanosine (8-OHdG), in subjects occupationally exposed to the metal. Male Pb-exposed workers (n = 236) from car battery manufacturing and recycling factories in Brazil participated in the study. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS and urinary 8-OHdG levels were measured by LC-MS/MS, and genotyping of HFE SNPs (rs1799945, C → G; and 1800562, G → A) was performed by TaqMan assays. Our data showed that carriers of at least one variant allele for HFE rs1799945 (CG + GG) tended to have higher PLL than those with the non-variant genotype (β = 0.34; p = 0.043); further, PLL was significantly correlated with the levels of urinary 8-OHdG (β = 0.19; p = 0.0060), while workers that carry the variant genotype for HFE rs1800562 (A-allele) showed a prominent increase in 8-OHdG, as a function of PLL (β = 0.78; p = 0.046). Taken together, our data suggest that HFE polymorphisms may modulate the Pb body burden and, consequently, the oxidative DNA damage induced by the metal.

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Section: Discussionmentioning

confidence: 83%