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.