Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.
Resumo: Introdução: Diante da pandemia ocasionada pelo vírus Sars-CoV-2, diversos profissionais da saúde depararam-se com novos desafios. Estudantes internos de Medicina também se encontram imersos nesse cenário e foram afetados no desempenho de seus papéis. Consiste este trabalho na observação dos aspectos físicos e psíquicos dos estudantes de Medicina que estão no período do internato nessa conjuntura. Objetivo: Desse modo, objetivou-se identificar os aprendizados e os impactos emocionais que os internos estão vivenciando no início de suas inserções no Sistema Único de Saúde diante da pandemia. Método: Para tanto, realizou-se uma análise qualitativa das narrativas de 37 internos de Medicina da Universidade Estadual do Ceará (23 do sexo masculino e 14 do sexo feminino), com média de idade de 25,5 anos, que responderam a um questionário eletrônico que lhes fora enviado como estratégia para auxiliar a coordenação do curso a organizar o internato no contexto pandêmico. Resultado: A relação dos internos com preceptores de Medicina foi destacada como causadora de sofrimento psíquico e carente de aprendizado antes e durante a pandemia. Observou-se a presença constante de sentimentos ambivalentes. Muitos dos internos de Medicina desejavam ajudar reconhecendo a importância de sua contribuição neste momento complexo da saúde no país. Todavia, alguns se sentiam inseguros com a situação crítica decorrente da pandemia, com receios acerca da segurança pessoal e familiar dos internos. Uma das razões pontuada foi a escassez de equipamentos de proteção individual (EPI). Conclusão: Vários internos ressaltaram o interesse em continuar o internato, e, por isso, é fundamental que os EPI estejam disponíveis para uso dos alunos. Diante do contexto de pandemia ou não, é imprescindível que o relacionamento entre preceptores e internos seja mais pedagógico e proporcione aprendizado aos estudantes. A apresentação desta experiência pode servir como recurso para a compreensão de cenários semelhantes, auxiliando a iluminar as relações do internato de Medicina que precisam passar por melhorias contínuas, quer em tempos de pandemia ou não, para favorecer a busca contínua por uma formação acadêmica de qualidade.
Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis.
Congenital Zika Syndrome (CZS) occurs in up to 42% of individuals exposed to ZIKV prenatally. Deregulation in gene expression and protein levels of components of the p53 signaling pathway, such as p53 and MDM2, due to ZIKV infection has been reported. Here, we evaluate functional polymorphisms in genes of the p53 signaling pathway as risk factors to CZS. Forty children born with CZS and forty-eight children exposed to ZIKV, but born without congenital anomalies were included in this study. Gestational and sociodemographic information as well as the genotypic and allelic frequencies of functional polymorphisms in TP53, MDM2, MIR605 and LIF genes were compared between the two groups. We found children with CZS exposed predominantly in the first trimester and controls in the third trimester (p<0.001). Moreover, children with CZS were predominantly from families with a lower socioeconomic level (p=0.008). We did not find a statistically significant association between the investigated polymorphisms and development of CZS; however, by comparing individuals with CZS and lissencephaly or without lissencephaly, we found a significative difference in the allelic frequencies of the TP53 rs1042522, which is associated with a more potent p53-induced apoptosis (p=0.007). Our findings suggest that the TP53 rs1042522 polymorphism should be better investigate as a genetic risk factor for the development of lissencephaly in children with CZS.
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