Associação entre polimorfismos em genes da via metabólica do ácido fólico e a exposição ao mercúrio em uma população ribeirinha do Baixo Tapajós

Abstract

Mercury (Hg) is considered one of the most dangerous metals for the environment and human health. High levels of Hg can contribute to the development of diseases and cause damage to the central nervous system. Glutathione (GSH) plays an important role in the toxicokinetics of Hg in the body. The formation of GSH occurs through the transsulfurization pathway of the homocysteine metabolic pathway, which uses folic acid as a source of methyl group for its proper functioning. Factors such as deficiency in folic acid consumption and polymorphisms in genes related to its metabolic pathway can indirectly interfere with GSH synthesis. Considering the relationship between folic acid and GSH, and the relationship of GSH in the toxicokinetics of Hg, the objective of this work was to evaluate whether there is an association between polymorphisms in genes of the folic acid metabolic pathway and exposure to Hg in residents of communities riverside of Baixo Tapajós. 166 residents of riverside communities in Baixo Tapajós, in Santarém (PA), were included. Mercury measurement was performed using atomic absorption spectrometry. Those who presented total Hg levels above those recommended by the WHO (>10 μL) were considered exposed; The majority of participants (85.5%) had Hg levels above the limit recommended by the WHO, among them (59.9%) had Hg levels between 10μg/L and 30 μg/L, 21.1% had levels of Hg between 31 μg/L and 50 μg/L and 19.0% had levels above 50μg/L, of which 6 were above 100μg/L. genotyping of the rs1801133 677C>T and rs2236225 c.1958G>A polymorphisms was performed using real-time PCR. The majority of individuals (85.5%) had Hg levels above those recommended by the WHO. As for the MTHFR gene, in the subgroup of those exposed to the homozygous wild genotype (CC) and homozygous mutant (TT), the frequencies were 30.6%, and the median Hg levels were 27.30 μg/L and 28.50 μg/ L, respectively. In the MTHFD1 gene, the genotypes that presented the highest frequency were: wild homozygous (GG) (45%) and mutant homozygous (AA) (26%). Furthermore, the GG genotype presented a higher median Hg concentration (29.98 μg/L). When jointly evaluating the dominant and recessive models, it was observed that the median Hg levels were higher among those who presented a dominant model for both polymorphisms (19.09 μg/L) compared to those who had the recessive model for both polymorphisms. polymorphisms (13.2 μg/L). An association was observed between the studied polymorphisms and Hg levels. The TT genotype (rs1801133 c.677C> of the MTHFR gene) and the TT/AA combination (double mutants) demonstrated an association with lower Hg levels, when compared to the wild-type double homozygous and heterozygous genotypes. However, more studies are still needed to better understand the effect of these and other genes in the folic acid metabolic pathway on Hg levels.