Abad Paloma, Pérez-Benavente Susana, Pérez-Luz Sara, Fobil Julius N, Kitenge Luyenga Batisseur, Kazadi Mukendi André, Puyet Antonio, Diez Amalia, Luzzatto Lucio, Azcárate Isabel G, Bautista José M
Department of Biochemistry and Molecular Biology, Universidad Complutense de Madrid, 28040 Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28041 Madrid, Spain.
One Health. 2025 Apr 25;20:101051. doi: 10.1016/j.onehlt.2025.101051. eCollection 2025 Jun.
Malaria has exerted potent selective pressure on the human genome over millennia and has been a significant force in shaping human evolution. We have determined in 424 individuals living in malaria-hyperendemic areas in Ghana and in the Democratic Republic of Congo, the genotypes at the loci , , , and . By qPCR we have also estimated parasitemia in all these subjects. We found that 41% of individuals tested had one protective variant, 20.5% two variants, 6.4% three variants, and 0.7% four variants. We have confirmed that , , and are associated with lower parasite density. The highest allele frequency was that of , approaching 0.2, and we found that it is in linkage disequilibrium with While overall malaria prevalence did not differ significantly among the groups, non-pregnant individuals with multiple protective alleles had lower rates of high-density parasitaemia, suggesting an additive effect of these variants against severe malaria infection, while pregnancy showed different allele protection profile. The high frequency of individuals carrying two or more protective polymorphisms might have implications for malaria transmission and parasite reservoir maintenance. Thus, the significance of additive or possibly synergistic effects of multiple protective genes co-existing in the same person deserves further investigation.
数千年来，疟疾一直在人类基因组上施加强大的选择压力，并且在塑造人类进化过程中发挥了重要作用。我们已经确定了生活在加纳和刚果民主共和国疟疾高度流行地区的424个人在、、和位点的基因型。通过定量聚合酶链反应（qPCR），我们还估算了所有这些受试者的疟原虫血症水平。我们发现，41%的受试个体有一个保护性变体，20.5%有两个变体，6.4%有三个变体，0.7%有四个变体。我们已经证实，、和与较低的寄生虫密度相关。最高的等位基因频率是，接近0.2，并且我们发现它与处于连锁不平衡状态。虽然各组之间的总体疟疾患病率没有显著差异，但具有多个保护性等位基因的非孕妇高密度疟原虫血症发生率较低，这表明这些变体对严重疟疾感染具有累加效应，而妊娠表现出不同的等位基因保护模式。携带两种或更多种保护性多态性的个体的高频率可能对疟疾传播和寄生虫库维持有影响。因此，同一个人体内共存的多个保护基因的累加或可能的协同效应的重要性值得进一步研究。
