Warimwe George M, Fegan Gregory, Kiragu Esther W, Musyoki Jennifer N, Macharia Alexander W, Marsh Kevin, Williams Thomas N, Bull Peter C
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
BMC Infect Dis. 2014 Sep 29;14:524. doi: 10.1186/1471-2334-14-524.
Host genotype accounts for a component of the variability in susceptibility to childhood Plasmodium falciparum malaria. However, despite numerous examples of host polymorphisms associated with tolerance or resistance to infection, direct evidence for an impact of host genetic polymorphisms on the in vivo parasite population is difficult to obtain. Parasite molecules whose expression is most likely to be associated with such adaptation are those that are directly involved in the host-parasite interaction. A prime candidate is the family of parasite var gene-encoded molecules on P. falciparum-infected erythrocytes, PfEMP1, which binds various host molecules and facilitates parasite sequestration in host tissues to avoid clearance by the spleen.
To assess the impact of host genotype on the infecting parasite population we used a published parasite var gene sequence dataset to compare var gene expression patterns between parasites from children with polymorphisms in molecules thought to interact with or modulate display of PfEMP1 on the infected erythrocyte surface: ABO blood group, haemoglobin S, alpha-thalassaemia, the T188G polymorphism of CD36 and the K29M polymorphism of ICAM1.
Expression levels of 'group A-like' var genes, which encode a specific group of PfEMP1 variants previously associated with low host immunity and severe malaria, showed signs of elevation among children of blood group AB. No other host factor tested showed evidence for an association with var expression.
Our preliminary findings suggest that host ABO blood group may have a measurable impact on the infecting parasite population. This needs to be verified in larger studies.
宿主基因型是儿童对恶性疟原虫疟疾易感性变异的一个组成部分。然而，尽管有许多与感染耐受性或抗性相关的宿主多态性实例，但很难获得宿主基因多态性对体内寄生虫种群产生影响的直接证据。其表达最有可能与这种适应性相关的寄生虫分子是那些直接参与宿主-寄生虫相互作用的分子。一个主要候选分子是恶性疟原虫感染红细胞上由寄生虫var基因编码的分子家族，即PfEMP1，它能结合各种宿主分子，并促进寄生虫在宿主组织中的滞留，以避免被脾脏清除。
为了评估宿主基因型对感染寄生虫种群的影响，我们使用了已发表的寄生虫var基因序列数据集，比较了来自儿童的寄生虫之间的var基因表达模式，这些儿童在被认为与感染红细胞表面PfEMP1的展示相互作用或调节其展示的分子中存在多态性：ABO血型、血红蛋白S、α地中海贫血、CD36的T188G多态性和ICAM1的K29M多态性。
编码一组特定PfEMP1变体（先前与低宿主免疫力和严重疟疾相关）的“A型样”var基因的表达水平，在AB血型儿童中显示出升高的迹象。所测试的其他宿主因素均未显示与var表达相关的证据。
我们的初步研究结果表明，宿主ABO血型可能对感染寄生虫种群有可测量的影响。这需要在更大规模的研究中得到验证。
