Polimorfismos dos Genes CD40, CD40L e BLYS, associados na co-estimulação dos Linfócitos B, em indivíduos naturalmente infectados pelo Plasmodium vivax na Amazônia Brasileira
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Data
2013-02-22
Autores
Capobianco, Marcela Petrolini [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Plasmodium vivax é a espécie mais prevalente de malária no Brasil. O processo co-evolutivo parasita-hospedeiro pode ser visto como uma ferramenta, na qual trocas genéticas adaptativas podem influenciar na diversidade da população. Objetivo: Investigar polimorfismos de genes envolvidos na resposta imune humoral visando identificar possíveis associações com a malária. Material e Métodos: a amostra foi constiuída por 103 pacientes com malária vivax não complicada e como grupo controle 97 indíviduos não-maláricos. A identificação dos SNPs –726T>C no gene CD40L, -1 C>T no gene CD40 e -871C>T no gene BLYS foram efetuadas pelo método de PCR-RFLP. As frequências genotípicas, alélicas e de indivíduos portadores de cada alelo foram estimadas por contagem direta. Também foram comparadas as frequências genotípicas observadas com as esperadas segundo o teorema de Hardy e Weinberg. Resultados: As freqüências genotípicas e alélicas para esses SNPs não diferiram estatisticamente entre pacientes e indivíduos do grupo controle. A combinação dos genótipos entre os genes CD40 e BLYS e entre CD40L e BLYS não revelou interação gênica na população estudada. Não foi observada associação entre resposta imune humoral e parasitemia nos indivíduos maláricos com os polimorfismos dos genes investigados. Ambos os genes se encontram em equilíbrio de Hardy e Weinberg. Conclusões: Os resultados deste estudo sugerem que as variantes genéticas analisadas nos genes CD40, CD40L e BLYS não afetam a funcionalidade das moléculas de modo que possa interferir na susceptibilidade a doença, mas estas variantes podem influenciar o curso clínico em vez de simplesmente aumentar ou diminuir a susceptibilidade
Plasmodium vivax is the most prevalent malaria species in Brazil. The parasite-host coevolutionary process can be viewed as an ‘arms race’, in which adaptive genetic changes in one are eventually matched by alterations in the other. Objectives: following the candidate gene approach we analyzed the CD40, CD40L and BLYS genes that participate in B-cell co-stimulation, for associations with P. vivax malaria. Methods: the study sample included 97 patients and 103 controls. We extracted DNA using the extraction and purification commercial kit and identified the following SNPs: -1C>T in the CD40 gene, –726T>C in the CD40L gene and the -871C>T in the BLyS gene using PCR-RFLP. We analyzed the genotype and allele frequencies by direct counting. We also compared the observed with the expected genotype frequencies using the Hardy-Weinberg Equilibrium. Results: The allele and genotype frequencies for these SNPs did not differ statistically between patient and control groups. Gene-gene interactions were not observed between the CD40 and BLYS and between the CD40L and BLYS genes. Overall, the genes were in Hardy-Weinberg Equilibrium. Significant differences were not observed among the frequencies of antibody responses against P. vivax sporozoite and erythrocytic antigens and the CD40 and BLYS genotypes Conclusions: the results of this study show that, although the investigated CD40, CD40L and BLYS alleles differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere in susceptibility to the disease. Significance: The variants of these genes may influence the clinical course rather than simply increase or decrease susceptibility
Plasmodium vivax is the most prevalent malaria species in Brazil. The parasite-host coevolutionary process can be viewed as an ‘arms race’, in which adaptive genetic changes in one are eventually matched by alterations in the other. Objectives: following the candidate gene approach we analyzed the CD40, CD40L and BLYS genes that participate in B-cell co-stimulation, for associations with P. vivax malaria. Methods: the study sample included 97 patients and 103 controls. We extracted DNA using the extraction and purification commercial kit and identified the following SNPs: -1C>T in the CD40 gene, –726T>C in the CD40L gene and the -871C>T in the BLyS gene using PCR-RFLP. We analyzed the genotype and allele frequencies by direct counting. We also compared the observed with the expected genotype frequencies using the Hardy-Weinberg Equilibrium. Results: The allele and genotype frequencies for these SNPs did not differ statistically between patient and control groups. Gene-gene interactions were not observed between the CD40 and BLYS and between the CD40L and BLYS genes. Overall, the genes were in Hardy-Weinberg Equilibrium. Significant differences were not observed among the frequencies of antibody responses against P. vivax sporozoite and erythrocytic antigens and the CD40 and BLYS genotypes Conclusions: the results of this study show that, although the investigated CD40, CD40L and BLYS alleles differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere in susceptibility to the disease. Significance: The variants of these genes may influence the clinical course rather than simply increase or decrease susceptibility
Descrição
Palavras-chave
Genetica humana, Polimorfismo (Genética), Malária, Plasmodium vivax, Human genetics
Como citar
CAPOBIANCO, Marcela Petrolini. Polimorfismos dos Genes CD40, CD40L e BLYS, associados na co-estimulação dos Linfócitos B, em indivíduos naturalmente infectados pelo Plasmodium vivax na Amazônia Brasileira. 2013. 56 f. Dissertação (mestrado) - Universidade Estadual Paulista Julio de Mesquita Filho. Instituto de Biociências, Letras e Ciências Exatas, 2013.