Impacto de polimorfismos em genes envolvidos na toxicidade do mercúrio e selênio, em comunidades amazônicas expostas aos elementos via dieta
Data
2024-03-21
Autores
Maraslis, Flora Troina 
Orientadores
Barcelos, Gustavo Rafael Mazzaron
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Tanto no ambiente quanto nos organismos vivos, existe uma complexa relação entre as formas elementar, orgânica e inorgânica do mercúrio. O metilmercúrio (forma orgânica - MeHg) é a forma com maior potencial de bioacumulação e o consumo de peixe é a principal fonte de exposição ao ser humano. Uma vez ingerido, a maior parte é absorvida e distribuída para todo o organismo, sendo o sistema nervoso central o principal órgão afetado. Comunidades em que os habitantes consomem pescados frequentemente, como os ribeirinhos da Amazônia brasileira, estão expostos a elevadas concentrações de metilmercúrio (MeHg). O selênio (Se), um elemento traço essencial ao organismo, é conhecido por contrapor os efeitos tóxicos do Hg, em parte, por meio das selenoproteínas que têm a selenocisteína incorporada na sequência de aminoácidos da proteína. O MeHg pode interagir e prejudicar o funcionamento de diversas moléculas devido à grande afinidade por grupos tiol (-SH) e selenol (-SeH) de proteínas e moléculas de baixo peso molecular. Os efeitos da exposição ao Hg não são homogêneos, sugerindo que características dos indivíduos podem alterar o padrão de resposta individual ao metal. Com isso, este estudo avaliou a influência de polimorfismos genéticos de GLRX rs2007 (C→G), GLRX2 rs912071 (C→T), TXNRD1 rs11111979 (C→G), TXNRD2 rs5748469 (C→A), MT1A rs11640851 (C→A), MT1M rs2270837 (A→G), MT2A rs10636 (G→C), SLC6A15 rs11116642 (C→T), SLC6A19 rs9418 (C→T), rs7732589 (G→A), SLC11A1 rs17235409 (G→A) e SLC11A2 rs149411 (A→ G), rs11169654 (C→T) sobre a concentração de Hg (Hg-s) e Se (Se-s) sanguíneo e plasmático (Hg-p e Se-p), espécies químicas de mercúrio no cabelo (Hg total, Hg orgânico e Hg inorgânico) e biomarcadores de estresse oxidativo de residentes ribeirinhos da região do rio Tapajós da Amazônia Brasileira. Residentes nessa região, que assinaram o TCLE, participaram de um grande estudo interdisciplinar, dos quais 365 participantes foram incluídos no presente estudo transversal. Foram utilizadas informações obtidas através de questionários sociodemográfico e de hábitos alimentares, além de medidas antropométricas. Amostras de sangue e cabelo foram utilizadas para dosagem de mercúrio. Amostras de sangue também foram utilizadas para avaliação dos biomarcadores de estresse oxidativo e submetidas à extração de DNA para avaliação dos polimorfismos propostos por PCR em tempo real. Os dados obtidos foram avaliados estatisticamente, por regressões lineares múltiplas considerando todos os indivíduos e nas estratificações por sexo, consumo de bebida alcoólica e fumo. Diversas associações foram observadas entre os polimorfismos estudados e as concentrações de Hg e Se nas diferentes matrizes biológicas e espécies químicas, e biomarcadores de estresse oxidativo. As análises com menores valores de p (com significância mantida após cálculo considerando múltiplas análises) foram observadas na estratificação por fumo. Indivíduos tabagistas que carregam o homozigoto CC para TXNRD1 apresentaram menores concentrações de Se-s do que aqueles com genótipo homozigoto GG (p<0,00010). Já, dentre os não tabagistas, participantes que têm o genótipo homozigoto CC para TXNRD2 têm menores concentrações de Hg-p (p=0,00035). Não tabagistas que carregam o genótipo homozigoto CC para GLRX2 apresentaram menor atividade de GPX (p=0,00014). Este estudo adiciona evidencia à literatura da modulação de Hg, Se e de biomarcadores de estresse oxidativo por polimorfismos genéticos.
Both in the environment and in living organisms, there is a complex relationship between the elemental, organic and inorganic forms of mercury. Methylmercury (organic form - MeHg) is the one with the greatest potential for bioaccumulation, and fish consumption is the main source of human exposure. Once ingested, most of it is absorbed and then distributed throughout the body, with the central nervous system being the main organ affected. Communities where inhabitants frequently consume fish, such as those living along the riverbanks of the Brazilian Amazon, are exposed to high concentrations of methylmercury (MeHg). Selenium (Se), an essential trace element for the body, is known to counteract the toxic effects of Hg, in part, through selenoproteins that have selenocysteine incorporated into the protein's amino acid sequence. MeHg can interact and impair several molecules functioning due to its great affinity for sulfhydryl (-SH) and selenohydryl (-SeH) groups of proteins and low molecular weight molecules. The Hg exposure effects are not homogeneous, suggesting that subject characteristics can alter the individual response pattern to the metal. Therefore, this study evaluated the influence of genetic polymorphisms of GLRX rs2007 (C→G), GLRX2 rs912071 (C→T), TXNRD1 rs11111979 (C→G), TXNRD2 rs5748469 (C→A), MT1A rs11640851 (C→A), MT1M rs2270837 (A→G), MT2A rs10636 (G→C), SLC6A15 rs11116642 (C→T), SLC6A19 rs9418 (C→T), rs7732589 (G→A), SLC11A1 rs17235409 (G→A) e SLC11A2 rs149411 (A→ G), rs11169654 (C→T) on the concentration of Hg (Hg-s) and Se (Se-s) in blood and plasma (Hg-p and Se-p), chemical species of mercury in the hair (total Hg, organic Hg and inorganic Hg) and oxidative stress biomarkers of riverside residents of the Tapajós River region of the Brazilian Amazon. People who signed the TCLE participated in a large interdisciplinary study, of which 365 participants were included in the present cross-sectional study. Information obtained through sociodemographic and eating habits questionnaires, in addition to anthropometric measurements, was used. Blood and hair samples were used for mercury measurement. Blood samples were also used to evaluate oxidative stress biomarkers and DNA extraction to evaluate polymorphisms by real-time PCR. The data obtained were statistically analyzed using multiple linear regressions considering all individuals and stratified by sex, alcohol consumption and smoking. Several associations were observed between the polymorphisms studied and the concentrations of Hg and Se in different biological matrices and chemical species, and biomarkers of oxidative stress. The analyzes with lower p values (with significance after multiple analyses estimate) were observed when stratifying by smoking. Smokers carrying the homozygous CC for TXNRD1 had lower Se-s concentrations than those with the homozygous GG genotype (p<0.00010). Among non-smokers, participants who have the homozygous CC genotype for TXNRD2 have lower Hg-p concentrations (p=0.00035). Non-smokers carrying the homozygous CC genotype for GLRX2 showed lower GPX activity (p=0.00014). This study adds evidence to the literature on the modulation of Hg, Se and biomarkers of oxidative stress by genetic polymorphisms.
Both in the environment and in living organisms, there is a complex relationship between the elemental, organic and inorganic forms of mercury. Methylmercury (organic form - MeHg) is the one with the greatest potential for bioaccumulation, and fish consumption is the main source of human exposure. Once ingested, most of it is absorbed and then distributed throughout the body, with the central nervous system being the main organ affected. Communities where inhabitants frequently consume fish, such as those living along the riverbanks of the Brazilian Amazon, are exposed to high concentrations of methylmercury (MeHg). Selenium (Se), an essential trace element for the body, is known to counteract the toxic effects of Hg, in part, through selenoproteins that have selenocysteine incorporated into the protein's amino acid sequence. MeHg can interact and impair several molecules functioning due to its great affinity for sulfhydryl (-SH) and selenohydryl (-SeH) groups of proteins and low molecular weight molecules. The Hg exposure effects are not homogeneous, suggesting that subject characteristics can alter the individual response pattern to the metal. Therefore, this study evaluated the influence of genetic polymorphisms of GLRX rs2007 (C→G), GLRX2 rs912071 (C→T), TXNRD1 rs11111979 (C→G), TXNRD2 rs5748469 (C→A), MT1A rs11640851 (C→A), MT1M rs2270837 (A→G), MT2A rs10636 (G→C), SLC6A15 rs11116642 (C→T), SLC6A19 rs9418 (C→T), rs7732589 (G→A), SLC11A1 rs17235409 (G→A) e SLC11A2 rs149411 (A→ G), rs11169654 (C→T) on the concentration of Hg (Hg-s) and Se (Se-s) in blood and plasma (Hg-p and Se-p), chemical species of mercury in the hair (total Hg, organic Hg and inorganic Hg) and oxidative stress biomarkers of riverside residents of the Tapajós River region of the Brazilian Amazon. People who signed the TCLE participated in a large interdisciplinary study, of which 365 participants were included in the present cross-sectional study. Information obtained through sociodemographic and eating habits questionnaires, in addition to anthropometric measurements, was used. Blood and hair samples were used for mercury measurement. Blood samples were also used to evaluate oxidative stress biomarkers and DNA extraction to evaluate polymorphisms by real-time PCR. The data obtained were statistically analyzed using multiple linear regressions considering all individuals and stratified by sex, alcohol consumption and smoking. Several associations were observed between the polymorphisms studied and the concentrations of Hg and Se in different biological matrices and chemical species, and biomarkers of oxidative stress. The analyzes with lower p values (with significance after multiple analyses estimate) were observed when stratifying by smoking. Smokers carrying the homozygous CC for TXNRD1 had lower Se-s concentrations than those with the homozygous GG genotype (p<0.00010). Among non-smokers, participants who have the homozygous CC genotype for TXNRD2 have lower Hg-p concentrations (p=0.00035). Non-smokers carrying the homozygous CC genotype for GLRX2 showed lower GPX activity (p=0.00014). This study adds evidence to the literature on the modulation of Hg, Se and biomarkers of oxidative stress by genetic polymorphisms.
Descrição
Citação
MARASLIS, Flora Troina. Impacto de polimorfismos em genes envolvidos na toxicidade do mercúrio e selênio, em comunidades amazônicas expostas aos elementos via dieta. 2024. 171 f. Tese (Doutorado Interdisciplinar em Ciências da Saúde) - Universidade Federal de São Paulo, Instituto de Saúde e Sociedade, Santos, 2024.