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

Abstract

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.