Polymorphisms in Genes Encoding Potential Mercury Transporters and Urine Mercury Concentrations in Populations Exposed to Mercury Vapor from Gold Mining.

Background: Elemental mercury (Hg0) is widely used in small-scale gold mining. Individuals working or living in mining areas have high urinary concentrations of Hg (U-Hg). Differences in genes encoding potential Hg-transporters may affect uptake and elimination of Hg. Objective: To identify single nucleotide polymorphisms (SNPs) in Hg-transporter genes that modify U-Hg. Methods: 1,017 men and women from Indonesia, the Philippines, Tanzania, and Zimbabwe were classified either as controls (no Hg exposure from gold mining) or as having low (living in a gold-mining area) or high exposure (working as gold miners). U-Hg was analyzed by cold-vapor atomic absorption spectrometry. Eighteen SNPs in eight Hg-transporter genes were analyzed. Results: U-Hg concentrations were higher among ABCC2/MRP2 rs1885301 A-allele carriers than among GG homozygotes in all populations, though differences were not statistically significant in most cases. MRP2 SNPs showed particularly strong associations with U-Hg in the subgroup with highest exposure (miners in Zimbabwe) where rs1885301 A-allele carriers had higher U-Hg than GG homozygotes (geometric mean (GM): 36.4 µg/g creatinine vs. 21.9; p=0.027), rs2273697 GG homozygotes had higher U-Hg than A-allele carriers (GM: 37.4 vs. 16.7; p=0.001), and rs717620 A-allele carriers had higher U-Hg than GG homozygotes (GM: 83 vs. 28; p=0.084). The SLC7A5/LAT1 rs33916661 GG genotype was associated with higher U-Hg in all populations (statistically significant for all Tanzanians combined). SNPs in SLC22A6/OAT1 (rs4149170) and SLC22A8/OAT3 (rs4149182) were associated with U-Hg mainly in the Tanzanian study groups. Conclusions: SNPs in putative Hg-transporter genes may influence U-Hg concentrations.