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Genetic Polymorphisms in Multispecific Transporters Mitigate Mercury Nephrotoxicity in an Artisanal and Small-Scale Gold Mining Community in Colombia.

ABSTRACT: In artisanal and small-scale gold mining, occupational exposure to mercury (Hg) vapor is related to harmful effects on several organs, including the kidneys. We previously reported significantly increased levels of Hg in blood and urine despite normal kidney function in individuals from Colombia occupationally exposed to Hg compared with those nonexposed. We evaluated the contribution of 4 genetic variants in key genes encoding the transporters solute carrier (SLC; rs4149170 and rs4149182) and ATP-binding cassette(ABC; rs1202169 and rs1885301) in the pathogenesis of nephrotoxicity due to Hg exposure in these groups. Regression analysis was performed to determine the association between the blood- and urine-Hg concentration with SLC and ABC polymorphisms in 281 Colombian individuals (160 exposed and 121 nonexposed to Hg). We found an enrichment of ABCB1 rs1202169-T allele in the exposed group (p = .011; OR= 2.05; 95% CI = 1.18-3.58) compared with the nonexposure group. We also found that carriers of SLC22A8 rs4149182-G and ABCB1 rs1202169-T alleles had a higher urinary clearance rate of Hg than noncarriers (β = 0.13, p = .04), whereas carriers of SLC22A6 rs4149170-A and ABCB1 rs1202169-C alleles showed abnormal levels of estimated glomerular filtration rate (β = -84.96, p = .040) and beta-2-microglobulin (β = 743.38, p < .001). Our results suggest that ABCB1 rs1202169 and its interaction with SLC22A8 rs4149182 and SLC22A6 rs4149170 could mitigate Hg nephrotoxicity by controlling the renal proximal tubule cell accumulation of inorganic Hg. This will be useful to estimate the risk of kidney toxicity associated to Hg and the genetic selection to aid adaptation to Hg-rich environments.

SUBMITTER: Sanchez Rodriguez LH

PROVIDER: S-EPMC7825076 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Gold mining is one of the major problems of contamination of hydric resources in Colombia, this practice generates a high impact on water quality due to the accumulation of waste during its process. In this study water quality was evaluated in five natural stream beds corresponding to four streams with gold mining operations and one in the Cauca River, taking samples before the water inlet and after the outlet in each operation in the streams of Dios Te Dé, Tamboral, Piedra Imán, and Lorenzo affected by artisanal gold mining labor, which drain into the Salvajina Reservoir on the Cauca River in the municipality of Suárez Cauca, Colombia. Characterization of water bodies in the streams was carried out applying contamination indices of Colombia. The IDEAM protocol was used as guide to monitor the water currents. Samples were taken in 15 stations in the natural stream beds with operations and a sampling station on the Cauca River after the reservoir in these lotic ecosystems, during three periods; two from 2018 and one from 2019. The range of the contamination indices according to the environmental variables were considered. Results show that the contaminants associated with TSS, TUR, and Hg are high in the sampling stations in the output of the operations and the sampling stations of the streams with influence on the operations (T3, T4, I2, I3, D2, and D5). The water quality score according to the ICA IDEAM index varied between acceptable and regular in the different sampling stations. However the Hg concentration in sampling station C1 of the Cauca River is due to contributions from the operations in the amalgamation process. This requires strategic interventions by the communities, miners, operation owners, and control organisms as the Regional Autonomous Corporation of Cauca (CRC) and the Ministry of Environment and Sustainable Development (MADS) to minimize the negative impacts on the hydric resource and ecosystemic services associated with this resource.

Project description:BACKGROUND: Artisanal small-scale gold mining (ASGM) is a poverty-driven activity practiced in over 70 countries worldwide. Zimbabwe is amongst the top ten countries using large quantities of mercury to extract gold from ore. This analysis was performed to check data availability and derive a preliminary estimate of disability-adjusted life years (DALYs) due to mercury use in ASGM in Zimbabwe. METHODS: Cases of chronic mercury intoxication were identified following an algorithm using mercury-related health effects and mercury in human specimens. The sample prevalence amongst miners and controls (surveyed by the United Nations Industrial Development Organization in 2004 and the University of Munich in 2006) was determined and extrapolated to the entire population of Zimbabwe. Further epidemiological and demographic data were taken from the literature and missing data modeled with DisMod II to quantify DALYs using the methods from the Global Burden of Disease (GBD) 2004 update published by the World Health Organization (WHO). While there was no disability weight (DW) available indicating the relative disease severity of chronic mercury intoxication, the DW of a comparable disease was assigned by following the criteria 1) chronic condition, 2) triggered by a substance, and 3) causing similar health symptoms. RESULTS: Miners showed a sample prevalence of 72% while controls showed no cases of chronic mercury intoxication. Data availability is very limited why it was necessary to model data and make assumptions about the number of exposed population, the definition of chronic mercury intoxication, DW, and epidemiology. If these assumptions hold, the extrapolation would result in around 95,400 DALYs in Zimbabwe's total population in 2004. CONCLUSIONS: This analysis provides a preliminary quantification of the mercury-related health burden from ASGM based on the limited data available. If the determined assumptions hold, chronic mercury intoxication is likely to have been one of the top 20 hazards for population health in Zimbabwe in 2004 when comparing with more than 130 categories of diseases and injuries quantified in the WHO's GBD 2004 update. Improving data quality would allow more accurate estimates. However, the results highlight the need to reduce a burden which could be entirely avoided.

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Genetic Polymorphisms in Multispecific Transporters Mitigate Mercury Nephrotoxicity in an Artisanal and Small-Scale Gold Mining Community in Colombia.

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