Mercury neurotoxicity is associated with polymorphisms in TNF-α and MMP-2 genes in the Munduruku indigenous population of the Brazilian Amazon

Exposure to mercury (Hg) is associated with neurological disorders. Polymorphisms in genes involved in the toxicokinetic and toxicodynamic of Hg may be associated with susceptibility to adverse neurological effects of Hg. This study examined the relationship between polymorphisms in TNF-α (rs1799964, rs1799724 and rs1800629), IL-6 (rs1800795) and MMP-2 (rs2285053) with Hg levels and neurological impact in the Munduruku indigenous population. A cross-sectional study was conducted in the Brazilian Amazon, analyzing 188 individuals for hair Hg levels, polymorphisms, and neurological alterations. Participants ranged in age from 0 to 72 years and the majority (50.8%) were male. The median Hg level was 6.9 µg/g (1.4-23.9 µg/g), with 97.4% of individuals having levels above the tolerable limit of ≥ 2.0 µg/g. A positive correlation was observed between fish consumption and higher Hg levels (p = 0.03). The genotypic frequencies of all polymorphisms were in Hardy-Weinberg equilibrium. Distal pinprick perception (p = 0.01) and foot mechanical detection threshold (p = 0.02) were positively associated with the TNF-α rs1799964, while toe amyotrophy was positively associated with the TNF-α rs1799724 polymorphism (p = 0.02). Distal thermal sensitivity abnormalities (p = 0.009) and distal pinprick perception (p = 0.034) were positively associated with the MMP-2 rs2285053 polymorphism. In conclusion, the TNF-α (rs1799964 and rs1799724) and MMP-2 (rs2285053) polymorphisms were associated with the neurotoxic effects of Hg in Brazilian indigenous populations. Integrating genetic analysis with environmental exposure monitoring can help to identify individuals who are more susceptible to selected neurological findings. This could improve public health strategies aimed at addressing the impact of Hg exposure, which has been dumped indiscriminately into the Amazon rivers due to illegal gold mining practices.