Laboratório de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, RJ, Brazil.
Infect Genet Evol. 2017 Dec;56:99-110. doi: 10.1016/j.meegid.2017.11.009. Epub 2017 Nov 10.
Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the genetic profile of the infected patient. However, the mechanisms that lead to severe disease and eventually death have not been determined, and a great challenge is the early identification of patients who are more likely to progress to a worse health condition. Studies performed in regions with cyclic outbreaks such as Cuba, Brazil, and Colombia have demonstrated that African ancestry confers protection against severe dengue. Highlighting the host genetics as an important factor in infectious diseases, a large number of association studies between genetic polymorphisms and dengue outcomes have been published in the last two decades. The most widely used approach involves case-control studies with candidate genes, such as the HLA locus and genes for receptors, cytokines, and other immune mediators. Additionally, a Genome-Wide Association Study (GWAS) identified SNPs associated with African ethnicity that had not previously been identified in case-control studies. Despite the increasing number of publications in America, Africa, and Asia, the results are quite controversial, and a meta-analysis is needed to assess the consensus among the studies. SNPs in the MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10 and PLCE1 genes are associated with the risk or protection of severe dengue, and the findings have been replicated in different populations. A thorough understanding of the viral, human genetic, and immunological mechanisms of dengue and how they interact is essential for effectively preventing dengue, but also managing and treating patients.
登革热是热带和亚热带地区的一个全球性主要问题；它由四种不同的病毒血清型引起，可表现为无症状、轻度或重度。许多因素相互作用决定疾病的严重程度，包括感染患者的遗传特征。然而，导致严重疾病并最终导致死亡的机制尚未确定，一个巨大的挑战是早期识别更有可能病情恶化的患者。在古巴、巴西和哥伦比亚等周期性暴发地区进行的研究表明，非洲血统对重症登革热具有保护作用。宿主遗传学作为传染病的一个重要因素被强调，在过去二十年中，已经发表了大量关于遗传多态性与登革热结果之间关联的研究。最广泛使用的方法是涉及候选基因（如 HLA 基因座和受体、细胞因子和其他免疫介质的基因）的病例对照研究。此外，全基因组关联研究 (GWAS) 确定了与非洲种族相关的 SNPs，这些 SNPs 以前在病例对照研究中没有被发现。尽管在美洲、非洲和亚洲的出版物数量不断增加，但结果却颇具争议，需要进行荟萃分析来评估研究之间的共识。MICB、TNF、CD209、FcγRIIA、TPSAB1、CLEC5A、IL10 和 PLCE1 基因中的 SNPs 与重症登革热的风险或保护相关，这些发现已在不同人群中得到复制。深入了解登革热的病毒、人类遗传和免疫学机制以及它们如何相互作用，对于有效预防登革热、管理和治疗患者至关重要。
