Department of Epidemiology, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
Department of Medicine, Imperial College of Science and Technology, London, UK.
Hum Genet. 2020 Jun;139(6-7):801-811. doi: 10.1007/s00439-020-02142-6. Epub 2020 Mar 4.
Malaria has been the pre-eminent cause of early mortality in many parts of the world throughout much of the last five thousand years and, as a result, it is the strongest force for selective pressure on the human genome yet described. Around one third of the variability in the risk of severe and complicated malaria is now explained by additive host genetic effects. Many individual variants have been identified that are associated with malaria protection, but the most important all relate to the structure or function of red blood cells. They include the classical polymorphisms that cause sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. More recently however, with improving technology and experimental design, others have been identified that include the Dantu blood group variant, polymorphisms in the red cell membrane protein ATP2B4, and several variants related to the immune response. Characterising how these genes confer their effects could eventually inform novel therapeutic approaches to combat malaria. Nevertheless, all together, only a small proportion of the heritable component of malaria resistance can be explained by the variants described so far, underscoring its complex genetic architecture and the need for continued research.
在过去的五千年中，疟疾一直是世界上许多地区早期死亡的主要原因，因此，它是迄今为止描述的对人类基因组选择压力最强的因素。现在，严重和复杂疟疾风险的可变性约有三分之一可以用宿主遗传效应的累加来解释。已经确定了许多与疟疾保护相关的个体变异，但最重要的都与红细胞的结构或功能有关。其中包括导致镰状细胞特征、α-地中海贫血、G6PD 缺乏症和主要红细胞血型变异的经典多态性。然而，最近随着技术和实验设计的改进，已经确定了其他一些与丹图血型变异、红细胞膜蛋白 ATP2B4 的多态性以及与免疫反应相关的几种变异有关的基因。描述这些基因如何赋予它们的作用，最终可能为对抗疟疾提供新的治疗方法。然而，迄今为止，通过描述的这些变异只能解释疟疾抗性的遗传成分的一小部分，这突显了其复杂的遗传结构和需要继续研究。
