The Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan.
Brighton and Sussex Centre for Global Health Research, Brighton and Sussex Medical School, Brighton, United Kingdom.
PLoS Negl Trop Dis. 2020 Apr 30;14(4):e0008053. doi: 10.1371/journal.pntd.0008053. eCollection 2020 Apr.
Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the infecting organism known as grains. Risk factors conferring susceptibility to mycetoma include environmental factors and pathogen factors such as virulence and the infecting dose, in addition to host factors such as immunological and genetic predisposition. Epidemiological evidence suggests that host genetic factors may regulate susceptibility to mycetoma and other fungal infections, but they are likely to be complex genetic traits in which multiple genes interact with each other and environmental factors, as well as the pathogen, to cause disease. This paper reviews what is known about genetic predisposition to fungal infections that might be relevant to mycetoma, as well as all studies carried out to explore host genetic susceptibility to mycetoma. Most studies were investigating polymorphisms in candidate genes related to the host immune response. A total of 13 genes had allelic variants found to be associated with mycetoma, and these genes lie in different pathways and systems such as innate and adaptive immune systems, sex hormone biosynthesis, and some genes coding for host enzymes. None of these studies have been replicated. Advances in genomic science and the supporting technology have paved the way for large-scale genome-wide association and next generation sequencing (NGS) studies, underpinning a new strategy to systematically interrogate the genome for variants associated with mycetoma. Dissecting the contribution of host genetic variation to susceptibility to mycetoma will enable the identification of pathways that are potential targets for new treatments for mycetoma and will also enhance the ability to stratify 'at-risk' individuals, allowing the possibility of developing preventive and personalised clinical care strategies in the future.
足菌肿是一种被严重忽视的热带病，其特征为皮下无痛性肿胀、多发性窦道和含有感染病原体（称为颗粒）聚集体的分泌物。易患足菌肿的危险因素包括环境因素和病原体因素，如毒力和感染剂量，以及宿主因素，如免疫和遗传易感性。流行病学证据表明，宿主遗传因素可能调节对足菌肿和其他真菌感染的易感性，但它们可能是复杂的遗传特征，其中多个基因相互作用以及环境因素和病原体共同导致疾病。本文综述了与足菌肿相关的可能与真菌感染有关的遗传易感性，以及为探索宿主对足菌肿的遗传易感性而进行的所有研究。大多数研究都在调查与宿主免疫反应相关的候选基因中的多态性。共有 13 个基因的等位基因变异与足菌肿相关，这些基因位于不同的途径和系统中，如先天和适应性免疫系统、性激素生物合成以及一些编码宿主酶的基因。这些研究均未得到重复验证。基因组科学的进步和支持技术为全基因组关联和下一代测序（NGS）研究铺平了道路，为系统地检测与足菌肿相关的基因组变异提供了新策略。剖析宿主遗传变异对足菌肿易感性的贡献，将能够确定潜在的治疗靶点，为足菌肿治疗提供新的方法，并增强对“高危”个体进行分层的能力，为未来开发预防和个性化临床护理策略提供可能。
