Polymorphisms in potential mercury transporter ABCC2 and neurotoxic symptoms in populations exposed to mercury vapor from goldmining

摘要

Background: Artisanal small-scale gold miners have high levels of mercury in human specimens often above recommended threshold values. There are differences reported in the manifestation of neurological symptoms of individuals with a comparable level of exposure to mercury, suggesting a genetic component influencing the susceptibility to mercury neurotoxicity. Objective: To investigate associations between polymorphisms (rs1885301, rs717620, rs2273697) in the potential Hg-transporter ABCC2 gene and neurological effects. Methods: 968 participants from the Philippines, Indonesia, Tanzania and Zimbabwe were included in this study (age 12-59 years). For the statistical analysis the countries were categorized into Africa (Philippines, Indonesia) and Asia (Tanzania, Zimbabwe). Study participants were from three exposure groups: without mercury exposure from goldmining (n = 129); living in mercury-contaminated areas (n = 281) and mercury working exposure (n = 558). To identify chronic inorganic mercury intoxication we applied a modified neurological score sum including eight binary coded parameters (from anamnestic, clinical and neurophysiological examinations). Associations between genotype and neurological score sum, as well as between genotype and separate neurological tests (ataxia of gait, dysdiadochokinesia, ataxia heel to shin, pencil tapping test and matchbox test) were evaluated. Results: We found that ABCC2 genotype were associated with performance on certain neurological tests: for rsl885301, A-allele carriers in the African populations showed significantly worse performance than GG carriers on the pencil tapping test; whereas for rs2273697, A-allele carriers in the African and Asian populations showed a significantly better performance than GG carriers on this test. When including an interaction term between genotype and exposure subgroup, interaction effects were also seen for the pencil tapping test and matchbox tests for rs2273697 in Asia. Conclusions: The results suggest that certain ABCC2 polymorphisms may influence the neurotoxic effects in mercury-burdened individuals. ABCC2 alleles associated with worse neurological performance in the present study. These alleles have previously been correlated with higher levels of urinary mercury concentrations in the same cohort. Taken together, these associations between ABCC2 genotype, mercury levels, and neurological effects support the hypothesis that some ABCC2 genotypes may have a higher neurotoxic potential, although further functional studies are needed to prove causation.