Influence of genetic polymorphisms of Hg metabolism and DNA repair on the frequencies of micronuclei, nucleoplasmic bridges, and nuclear buds in communities living in gold mining areas.

Fishing communities living near gold mining areas are at increased risk of mercury (Hg) exposure via bioaccumulation of methylmercury (MeHg) in fish. This exposure has been linked to health effects that may be triggered by genotoxic events. Genetic polymorphisms play a role in the risk associated with Hg exposure. This study evaluated the effect of single nucleotide polymorphisms (SNPs) in metabolic and DNA repair genes on genetic instability and total hair Hg (T-Hg) levels in 78 individuals from "La Mojana" in northern Colombia and 34 individuals from a reference area. Genetic instability was assessed by the frequency of micronuclei (MNBN), nuclear buds (NBUDS), and nucleoplasmic bridges (NPB). We used a Poisson regression to assess the influence of SNPs on T-Hg levels and genetic instability, and a Bayesian regression to examine the interaction between Hg detoxification and DNA repair. Among exposed individuals, carriers of XRCC1 _Arg399Gln had a significantly higher frequency of MNBN. Conversely, the XRCC1 _Arg194Trp and OGG1 _Ser326Cys polymorphisms were associated with lower frequencies of MNBN. XRCC1 _Arg399Gln , XRCC1 _Arg280His , and GSTM1 _Null carriers showed lower NPB frequencies. Our results also indicated that individuals with the GSTM1 _Null and GSTT1 _null polymorphisms had a 1.6-fold risk for higher T-Hg levels. The Bayesian model showed increased MNBN frequencies in carriers of the GSTM1 _Null polymorphism in combination with XRCC1 _Arg399Gln and increased NBUDS frequencies in the GSTM1 _Null carriers with the XRCC3 _Thr241Met and OGG1 _Ser326Cys alleles. The GSTM1 ₊ variant was found to be a protective factor in individuals carrying OGG1 _Ser326Cys (MNBN) and XRCC1 _Arg280His (NPB); the GSTT1 ₊ polymorphism combined with XRCC _Arg194Trp also modulated lower MNBN frequencies, while GSTT1 ₊ carriers with the XRCC1 _Arg399Gln allele showed lower NPB frequencies. Consistent with GSTM1, GSTT1 _Null carriers with XRCC3 _Thr241Met showed increased NBUDS frequency. With the rise of gold mining activities, these approaches are vital to identify and safeguard populations vulnerable to Hg's toxic effects.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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