Kwiatkowski D
Oxford University Department of Paediatrics, John Radcliffe Hospital, UK.
Parassitologia. 1999 Sep;41(1-3):233-40.
It is poorly understood why some malarial infections are fatal while others resolve without complications. Host genetic factors are partly responsible. More than ten specific susceptibility determinants have already been defined, including both structural and regulatory polymorphisms of erythyrocytes and of the immune system, and it is likely that many more have yet to be discovered. A vast number of DNA polymorphisms, scattered throughout the human genome, cause individual variation in probably all immunological and biochemical processes. Advances in DNA technology offer the prospect of screening thousands of candidate genes for association with susceptibility to severe malaria in large multicentre case-control and family-based studies. Saturation mapping of candidate gene regions, combined with cellular and molecular analysis of disease-associated polymorphisms, is essential for understanding the functional basis of the genetic associations that such an exercise will generate. This information will pinpoint critical molecular pathways in immunity and pathogenesis and may lead to fundamentally new strategies for treatment and prevention of severe malaria.
目前尚不清楚为何有些疟疾感染会致命，而另一些则可无并发症地痊愈。宿主遗传因素是部分原因。已经确定了十多种特定的易感性决定因素，包括红细胞和免疫系统的结构及调节多态性，而且很可能还有更多因素有待发现。遍布人类基因组的大量DNA多态性可能在所有免疫和生化过程中导致个体差异。DNA技术的进展为在大型多中心病例对照研究和基于家庭的研究中筛选数千个与严重疟疾易感性相关的候选基因提供了可能。对候选基因区域进行饱和定位，并结合对疾病相关多态性的细胞和分子分析，对于理解此类研究将产生的遗传关联的功能基础至关重要。这些信息将确定免疫和发病机制中的关键分子途径，并可能带来治疗和预防严重疟疾的全新策略。
