Parnaiba Delta Federal University (UFDPar), Parnaiba, Piaui, Brazil; Laboratory of Biology of Microorganisms, Parnaiba Delta Federal University (UFDPar), Parnaiba, Piaui, Brazil.
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
Cytokine. 2022 Sep;157:155955. doi: 10.1016/j.cyto.2022.155955. Epub 2022 Jul 2.
Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10 and 10 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.
登革热是由登革病毒（DENV）感染引起的一种临床表现，其特征为强烈的宿主免疫反应，伴有高热、厌食、头痛和肌肉疼痛。几种免疫介质参与了 DENV 感染的病理生理学过程，其中免疫分子基因的多态性与感染的易感性和严重程度有关。已经有几项荟萃分析发现了免疫介质基因遗传变异与登革热之间的显著关联，但这些结果可能是假阳性的。因此，为了解决这个问题，我们采用贝叶斯方法进行了系统的重新评估，以验证这些结果中的假阳性率。对上述问题的荟萃分析研究进行了系统搜索。计算了假阳性报告概率（FPRP）和贝叶斯假发现概率（BFDP）在先验概率为 10 和 10 的情况下的值。为了验证纳入研究的方法学质量，应用了威尼斯标准进行评估。此外，还设计了基因-基因和蛋白质-蛋白质网络。结果，纳入了七项关于几种免疫炎症介质基因遗传变异与 DENV 感染的荟萃分析。只有 TNF、MICB、PLCE1、VDR、CD32 和 HLA-A 基因的多态性被认为是值得注意的。威尼斯标准的结果存在异质性，表明方法学质量存在差异。基因-基因和蛋白质-蛋白质网络表明这些免疫介质是疾病的重要参与者。我们建议这些多态性作为 DENV 发病机制和免疫反应的潜在生物标志物。
