Análise comparativa das frequências alélicas e genotípicas dos polimorfismos da Glicose-6-fosfato desidrogenase em pacientes com malária vivax e indivíduos não maláricos de áreas endêmicas no Brasil
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Data
2018-03-01
Autores
Orlandini, Letícia Cardoso
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A glicose-6-fosfato desidrogenase (G6PD) é uma enzima metabólica e citoplasmática de importante papel na prevenção de danos oxidativos. Nos glóbulos vermelhos sua ausência é prejudicial à célula, devido à falta da maioria das organelas celulares e à sensibilidade ao estresse oxidativo. A deficiência da enzima G6PD (G6PDd) é, em geral, assintomática. Porém, fatores como a utilização da primaquina, de alto potencial hemolítico, no tratamento da malária vivax, podem levar o portador da deficiência a uma anemia hemolítica aguda. O gene G6PD apresenta vários sítios polimórficos, com cerca de 217 mutações e mais de 400 variantes bioquímicas significativas descritas. As variantes A- e Mediterrânea são encontradas com frequências consideráveis mundialmente, sendo essas variantes caracterizadas por redução considerável na atividade enzimática. No Brasil, devido à ausência de testes de rotina para detecção de G6PDd e a utilização de primaquina como droga principal de combate a malária vivax, responsável por cerca de 90% dos casos na região Amazônica Brasileira, faz-se necessário conhecer a frequência de G6PDd A- para implantação de novas estratégias a fim de melhorar a segurança no tratamento e reduzir o número de transfusões sanguíneas. Assim, o estudo avaliou a frequência da variante A- por PCRRFLP em 476 indivíduos, 200 maláricos e 276 não maláricos, procedentes de áreas endêmicas de malária vivax na Região Norte do país. Após as análises, foram encontrados 14 indivíduos com a G6PDd A-, o que corresponde a 2,94% das amostras avaliadas, sendo seis indivíduos do grupo de maláricos e oito indivíduos do grupo controle. Esta frequência se encontra próxima ao que é relatado em outros estudos na região Norte. Porém, não houve diferenças significativas entre a frequência dos genótipos entre os grupos de estudo e entre as regiões avaliadas, de forma que, a associação entre a presença da mutação e as chances da infecção de malária se estabelecer e da doença se desenvolver em cada grupo de estudo e em cada região apresentam resultados divergentes e reforçam a necessidade de maiores investigações. Por fim, o cenário observado neste estudo, ressalta a importância do diagnóstico preciso da G6PDd em populações multiétnicas antes da administração de drogas antimaláricas de elevado potencial hemolítico, a fim de contribuir com a segurança do tratamento e a erradicação da malária na Região endêmica Brasileira.
Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic and cytoplasmic enzyme of important role in preventing oxidative damage. In red blood cells their absence is detrimental to the cell, due to the lack of most cellular organelles and the sensitivity to oxidative stress. Deficiency of the enzyme G6PD (G6PDd) is generally asymptomatic. However, factors such as the use of primaquine with a high hemolytic potential for treatment of vivax malaria, can lead the person with the deficiency to an acute hemolytic anemia. The G6PD gene has several polymorphic sites, with about 217 mutations and more than 400 significant biochemical variants described. The A- and Mediterranean variants are found with considerable frequencies worldwide, that variants being characterized by a considerable reduction in the enzymatic activity. In Brazil, is necessary to know the frequency of G6PDd A- to implement new strategies to improve treatment safety and reduce the number of blood transfusions, due to the absence of routine tests to detect G6PDd and the use of primaquine as the main drug to combat vivax malaria, responsible for about 90% of the cases in the Brazilian Amazon region. Thus, the frequency of the A-variant was evaluated by PCR-RFLP in 476 individuals, 200 malaria and 276 non malaria, from endemic areas of vivax malaria in the Northern Region of the country. After the analysis, 14 individuals were found with G6PDd A-, which corresponds to 2.94% of the samples evaluated, six of which were individuals from the malaria group and eight from the control group. This frequency is close to what is reported in other studies in the Northern region. However, there were no significant differences between the genotype frequency between the study groups and between the evaluated regions, so the association between the presence of the mutation and the chances of malaria infection was established and the disease developed in each group in each region present divergent results and reinforce the need for further investigation. Finally, the scenario observed in this study underscores the importance of accurate diagnosis of G6PDd in multiethnic populations prior to the administration of antimalarial drugs of high hemolytic potential, in order to contribute to the safety of treatment and eradication of malaria in the Brazilian endemic region.
Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic and cytoplasmic enzyme of important role in preventing oxidative damage. In red blood cells their absence is detrimental to the cell, due to the lack of most cellular organelles and the sensitivity to oxidative stress. Deficiency of the enzyme G6PD (G6PDd) is generally asymptomatic. However, factors such as the use of primaquine with a high hemolytic potential for treatment of vivax malaria, can lead the person with the deficiency to an acute hemolytic anemia. The G6PD gene has several polymorphic sites, with about 217 mutations and more than 400 significant biochemical variants described. The A- and Mediterranean variants are found with considerable frequencies worldwide, that variants being characterized by a considerable reduction in the enzymatic activity. In Brazil, is necessary to know the frequency of G6PDd A- to implement new strategies to improve treatment safety and reduce the number of blood transfusions, due to the absence of routine tests to detect G6PDd and the use of primaquine as the main drug to combat vivax malaria, responsible for about 90% of the cases in the Brazilian Amazon region. Thus, the frequency of the A-variant was evaluated by PCR-RFLP in 476 individuals, 200 malaria and 276 non malaria, from endemic areas of vivax malaria in the Northern Region of the country. After the analysis, 14 individuals were found with G6PDd A-, which corresponds to 2.94% of the samples evaluated, six of which were individuals from the malaria group and eight from the control group. This frequency is close to what is reported in other studies in the Northern region. However, there were no significant differences between the genotype frequency between the study groups and between the evaluated regions, so the association between the presence of the mutation and the chances of malaria infection was established and the disease developed in each group in each region present divergent results and reinforce the need for further investigation. Finally, the scenario observed in this study underscores the importance of accurate diagnosis of G6PDd in multiethnic populations prior to the administration of antimalarial drugs of high hemolytic potential, in order to contribute to the safety of treatment and eradication of malaria in the Brazilian endemic region.
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Palavras-chave
G6PDd, Variante A-, Plasmodium vivax, Anemia