Abstract
Mercury (Hg) vapor can produce kidney injury, where the proximal tubule region of the nephron is the main target of the Hg-induced oxidative stress. Hg is eliminated from the body as a glutathione conjugate. Thus, single nucleotide polymorphisms (SNPs) in glutathione-related genes might modulate the negative impact of this metal on the kidneys. Glutathione-related SNPs were tested for association with levels of Hg and renal function biomarkers between occupationally exposed (n = 160) and non-exposed subjects (n = 121). SNPs were genotyped by TaqMan assays in genomic DNA samples. Total mercury concentration was measured in blood, urine and hair samples. Regression analyses were performed to estimate the effects of SNPs on quantitative traits. Alleles GCLM rs41303970-T and GSTP1 rs4147581-C were significantly overrepresented in the exposed compared with the non-exposed group (P < 0.01). We found significant associations for GCLM rs41303970-T with higher urinary clearance rate of Hg (β = 0.062, P = 0.047), whereas GCLC rs1555903-C was associated with lower levels of estimated glomerular filtration rate in the non-exposed group (eGFR, β = − 3.22, P = 0.008) and beta-2-microglobulin in the exposed group (β-2MCG, β = − 19.32, P = 0.02). A SNP-SNP interaction analysis showed significant epistasis between GSTA1 rs3957356-C and GSS rs3761144-G with higher urinary levels of Hg in the exposed (β = 0.13, P = 0.04) but not in the non-exposed group. Our results suggest that SNPs in glutathione-related genes could modulate the pathogenesis of Hg nephrotoxicity in our study population by modulating glutathione concentrations in individuals occupationally exposed to this heavy metal.
Highlights
Mercury (Hg) vapor can produce kidney injury, where the proximal tubule region of the nephron is the main target of the Hg-induced oxidative stress
The aim of the current work was to investigate whether single nucleotide polymorphisms (SNPs) in the genes glutamate-cysteine ligase catalytic subunit (GCLC); glutamate-cysteine ligase modifier subunit (GCLM); glutathione synthetase (GSS); glutathione S-transferase alpha 1 (GSTA1); and glutathione S-transferase pi 1 (GSTP1) are associated with modulation of Hg nephrotoxicity in our gold mining population in Colombia
Our study suggests that SNPs in glutathione-related genes might influence toxic effects of Hg by modulating glutathione concentrations in individuals occupationally exposed to this heavy metal
Summary
Mercury (Hg) vapor can produce kidney injury, where the proximal tubule region of the nephron is the main target of the Hg-induced oxidative stress. The gene-Hg interactions have not been reported in relation to kidney injury, which needs to be addressed in order to understand the impact of genetic variation on health effects caused by this heavy metal In this context, we carried out an epidemiological study on occupational exposure to Hg vapor on kidney function in a historically gold-mining town in Colombia. We reported that, despite higher levels of Hg in blood and urine in miners compared to a control group, the kidney function was normal and comparable between both groups[20] This is especially interesting since it has been reported that SNPs in detoxification genes are associated with toxic metal tolerance and adaptation in humans[21]. We hypothesized that genetic variants in glutathione-related genes could modulate the negative impact of Hg on the kidneys
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