Verra F, Mangano V D, Modiano D
Department of Public Health, University of Rome La Sapienza, Rome, Italy.
Parasite Immunol. 2009 May;31(5):234-53. doi: 10.1111/j.1365-3024.2009.01106.x.
Plasmodium falciparum represents one of the strongest selective forces on the human genome. This stable and perennial pressure has contributed to the progressive accumulation in the exposed populations of genetic adaptations to malaria. Descriptive genetic epidemiology provides the initial step of a logical procedure of consequential phases spanning from the identification of genes involved in the resistance/susceptibility to diseases, to the determination of the underlying mechanisms and finally to the possible translation of the acquired knowledge in new control tools. In malaria, the rational development of this strategy is traditionally based on complementary interactions of heterogeneous disciplines going from epidemiology to vaccinology passing through genetics, pathogenesis and immunology. New tools including expression profile analysis and genome-wide association studies are recently available to explore the complex interactions of host-parasite co-evolution. Particularly, the combination of genome-wide association studies with large multi-centre initiatives can overcome the limits of previous results due to local population dynamics. Thus, we anticipate substantial advances in the interpretation and validation of the effects of genetic variation on malaria susceptibility, and thereby on molecular mechanisms of protective immune responses and pathogenesis.
恶性疟原虫是人类基因组面临的最强选择压力之一。这种持续稳定的压力促使暴露人群中对疟疾的遗传适应性逐渐积累。描述性遗传流行病学是一个逻辑程序的初始步骤，该程序包括多个连续阶段，从识别与疾病抗性/易感性相关的基因，到确定潜在机制，最终将获得的知识转化为新的控制工具。在疟疾研究中，这一策略的合理发展传统上基于从流行病学到疫苗学等多学科的互补性相互作用，其中涉及遗传学、发病机制和免疫学。最近出现了包括表达谱分析和全基因组关联研究在内的新工具，用于探索宿主-寄生虫共同进化的复杂相互作用。特别是，全基因组关联研究与大型多中心项目的结合可以克服以往因当地人群动态变化而导致的研究结果局限性。因此，我们预计在解释和验证基因变异对疟疾易感性的影响方面将取得重大进展，进而在保护性免疫反应和发病机制的分子机制方面取得进展。
