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Determinação do polimorfismo da enzima GSTP1 em trabalhadores expostos à sílica e associação com silicose / Determination of enzyme GSTP1 polymorphism in workers exposed to silica and association with silicosis

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Previous issue date: 2010 / A sílica é um composto natural formado pelos dois elementos mais abundantes na Terra - oxigênio e silício. A exposição a partículas de sílica cristalina induz a uma inflamação pulmonar crônica, que pode evoluir para fibrose pulmonar, acarretando na doença conhecida como silicose. O estresse oxidativo desempenha um papel importante na patogênese desta fibrose pulmonar. Sendo assim, a expressão de genes antioxidantes, como glutationa S-transferases (GSTs), são importantes componentes de proteção das células contra o estresse oxidativo e são conhecidas como genes altamente polimórficos, podendo contribuir para a susceptibilidade a silicose. O polimorfismo da GSTP1 A/G resulta na substituição do aminoácido isoleucina por valina, diminuindo, substancialmente, a atividade da enzima GSTP1. O estudo teve como objetivo a determinação do polimorfismo da enzima GSTP1 em trabalhadores expostos à sílica e associação com silicose. A população foi composta por 82 trabalhadores expostos à sílica oriundos, principalmente, da indústria naval. O polimorfismo da GSTP1 foi analisado por PCR-RFLP. Como resultado verificou-se que 31,6 por cento dos trabalhadores tinham genótipo A/A, 57,9 por cento A/G e 10,5 por cento G/G. Observou-se que a média da atividade enzimática da GST foi menor (1,58 U/mL enzima) em indivíduos com o alelo G em relação ao alelo A (1,84 U/mL de enzima). Trabalhadores expostos à sílica portadores do alelo G mostraram um maior risco de desenvolver silicose, embora os resultados não tenham sido significativos, provavelmente, em função do universo amostral. Os indivíduos portadores do alelo G tiveram níveis menores na atividade da GST, independente do genótipo das enzimas GSTM1 e GSTT1. Em conclusão, estudos adicionais devem ser realizados para determinar o polimorfismo da GSTP1 em populações expostas à sílica em comparação com populações não-expostas, pois os resultados deste trabalho sugerem a utilização da determinação do polimorfismo da GSTP1, no processo de avaliação da exposição à sílica, como uma ferramenta complementar na identificação de subgrupos mais susceptíveis ao desenvolvimento da doença silicose. / Sílica is the natural compound of the two most abundant elements on Earth - oxygen and silicon.
Exposure to crystalline silica particles induces chronic lung inflammation, which may progress to
lung fibrosis, a disease known as silicosis. The oxidative stress plays an important role in the
pathogenesis of pulmonary fibrosis. In this respect, the expression of antioxidant genes such as
glutathione S-transferases (GSTs) are important to protect cells from oxidative stress and they are
known as highly polymorphic genes, that may contribute to silicosis susceptibility. The GSTP1
A G polymorphism results in amino acid substitution isoleucine for valine which substantially
diminishes GSTP1 enzyme activity. The objetive of study was the determination of enzyme
GSTP1 polymorphism in workers exposed to silica and association with silicosis. The population
was composed of 82 workers exposed to silica coming mainly from the shipbuilding
industry.GSTP1 polymorphism was analyzed by PCR-RFLP. As a result it was found that 31,6%
of workers had genotype A/A, 57,9% A/G and 10.5% G/G. It was observed that the mean
enzyme activity of GST was lower (1.58 U / mL enzyme) in individuals with allele G compared
with allele A (1.84 U / mL enzyme). Workers exposed to silica with allele G showed a higher risk
of developing silicosis, although the results had not been significant, probably because of sample
size. Individuals with allele G had lower levels of GST activity, independent of the genotype of
GSTM1 and GSTT1 enzymes. In conclusion, further studies to determine the polymorphism of
GSTP1 should be conducted in populations exposed to silica compared with non-exposed
populations, because the results in this paper suggest the use of the determination of the
polymorphism of GSTP1, in the process of evaluating the exposure to silica, as a complementary
tool in the identification of subgroups more likely to develop the disease silicosis. / Sílica is the natural compound of the two most abundant elements on Earth - oxygen and silicon.
Exposure to crystalline silica particles induces chronic lung inflammation, which may progress to
lung fibrosis, a disease known as silicosis. The oxidative stress plays an important role in the
pathogenesis of pulmonary fibrosis. In this respect, the expression of antioxidant genes such as glutathione S-transferases (GSTs) are important to protect cells from oxidative stress and they are known as highly polymorphic genes, that may contribute to silicosis susceptibility. The GSTP1 A G polymorphism results in amino acid substitution isoleucine for valine which substantially diminishes GSTP1 enzyme activity. The objetive of study was the determination of enzyme GSTP1 polymorphism in workers exposed to silica and association with silicosis. The population was composed of 82 workers exposed to silica coming mainly from the shipbuilding
industry.GSTP1 polymorphism was analyzed by PCR-RFLP. As a result it was found that 31,6%
of workers had genotype A/A, 57,9% A/G and 10.5% G/G. It was observed that the mean enzyme activity of GST was lower (1.58 U / mL enzyme) in individuals with allele G compared with allele A (1.84 U / mL enzyme). Workers exposed to silica with allele G showed a higher risk of developing silicosis, although the results had not been significant, probably because of sample size. Individuals with allele G had lower levels of GST activity, independent of the genotype of GSTM1 and GSTT1 enzymes. In conclusion, further studies to determine the polymorphism of GSTP1 should be conducted in populations exposed to silica compared with non-exposed populations, because the results in this paper suggest the use of the determination of the polymorphism of GSTP1, in the process of evaluating the exposure to silica, as a complementary tool in the identification of subgroups more likely to develop the disease silicosis.

Identiferoai:union.ndltd.org:IBICT/oai:www.arca.fiocruz.br:icict/2528
Date January 2010
CreatorsRocha, Daniele Ramos
ContributorsMattos, José Carlos Pelielo de, Castro, Hermano Albuquerque de, Mattos, José Carlos Pelielo de, Castro, Hermano Albuquerque de, Araújo, Adriano Caldeira de, Sarcinelli, Paula de Novaes, Mattos, Rita
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Sourcereponame:Repositório Institucional da FIOCRUZ, instname:Fundação Oswaldo Cruz, instacron:FIOCRUZ
Rightsinfo:eu-repo/semantics/openAccess

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