RESUMO
ABSTRACT INTRODUCTION: Venous thrombosis is a multifactor disease with high incidence in the population. The development of this disease is closely linked to the presence of environmental and genetic factors and may occur in combination or alone. Among the various genetic mutations that may predispose to a thrombotic event, the most frequent in the population is the G1691A mutation in clotting factor V, known as factor V Leiden (FVL). This mutation brings the phenotype known as activated protein C resistance, leading to a hypercoagulable state, which increases the risk of thrombosis. OBJECTIVE: To investigate the presence of FVL in individuals with history of venous thrombosis, and as the control group, individuals with no history of the disease. METHOD: The method used was the polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). RESULTS: The results showed mutation prevalence of 21.5% in heterozygosity in patient group; no individuals with mutated homozygous were identified. The results also showed a high recurrence rate among the mutation carriers. CONCLUSION: In conclusion, the research of mutation on factor V has strong impact on investigation of venous thromboembolism, in order to elucidate the etiology of the event, and in treatment and in prophylaxis against the recurrence.
RESUMO INTRODUÇÃO: A trombose venosa é uma doença de caráter multifatorial e de alta incidência na população. O desenvolvimento dessa patologia está intimamente ligado à presença de fatores ambientais e genéticos, podendo ocorrer em associação ou isoladamente. Entre as diversas mutações genéticas que podem predispor a um evento trombótico, a de maior ocorrência na população é a mutação G1691A no fator V da coagulação, conhecida como fator V de Leiden (FVL). Essa mutação provoca o fenótipo conhecido como resistência à proteína C ativada, levando a um quadro de hipercoagulabilidade, que aumenta o risco de trombose. OBJETIVO: Investigar a presença do FVL em indivíduos com histórico de trombose venosa e, como grupo-controle, indivíduos sem histórico. MÉTODO: A metodologia utilizada foi a técnica de reação em cadeia da polimerase (PCR), seguida de polimorfismo no comprimento dos fragmentos de restrição (RFLP). RESULTADOS: Os resultados mostraram prevalência da mutação de 21,5% em heterozigose entre o grupo de pacientes; não foram identificados indivíduos homozigotos mutados. Os resultados também apresentaram alto índice de recorrência entre os portadores da mutação. CONCLUSÃO: Conclui-se que a pesquisa da mutação do fator V tem forte impacto na investigação do tromboembolismo venoso a fim de elucidar a etiologia do evento, além de auxiliar no tratamento e na profilaxia diante da recorrência.
RESUMO
BACKGROUND: Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil. METHODS: Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection. RESULTS: GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity. CONCLUSION: Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population.
