Tinto Halidou, Ouédraogo Jean Bosco, Erhart Annette, Van Overmeir Chantal, Dujardin Jean-Claude, Van Marck Eric, Guiguemdé Tinga Robert, D'Alessandro Umberto
Institut de Recherche en Sciences de la Santé, Bobo Dioulasso, Burkina Faso.
Infect Genet Evol. 2003 Nov;3(4):287-92. doi: 10.1016/j.meegid.2003.08.002.
The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in Plasmodium falciparum was explored in samples from patients with uncomplicated malaria and tested in vitro and in vivo with chloroquine (CQ) in Burkina Faso. The two mutations were strongly related. The Pfcrt T76 mutation was found in 82% of the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half (16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1 Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the presence of the Pfcrt T76 mutation. This suggests that the occurrence of the Pfmdr-1 Y86 mutation is dependent on that of Pfcrt T76 mutation and could explain previous reports linking the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild (WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50 geometric mean (GMIC50) values, while those carrying both Pfcrt T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single mutant Pfcrt T76 (MW) had the highest. Among pre-treatment samples there was a strong linkage disequilibrium with an excess of MM and WW and a deficit of single mutants (MW and WM), suggesting that parasite fitness is higher for the former and lower for the latter.
在布基纳法索，对非重症疟疾患者的样本进行研究，探讨恶性疟原虫中Pfcrt T76与Pfmdr-1 Y86突变之间的关系，并在体外和体内用氯喹（CQ）进行测试。这两种突变密切相关。在也具有Pfmdr-1 Y86突变的样本中，82%发现有Pfcrt T76突变（优势比（OR）=4.8 [95%置信区间：1.7 - 13.3]；P = 0.002）。然而，具有Pfcrt T76突变的样本中只有一半（16/34）也具有Pfmdr-1 Y86突变。后者显然与体外耐药性相关（OR = 4.8 [95%置信区间：1.4 - 16.5]；P = 0.01），但在对Pfcrt T76突变的存在进行校正后，这种关联消失了（P = 0.77）。这表明Pfmdr-1 Y86突变的发生依赖于Pfcrt T76突变，并且可以解释先前将Pfmdr-1 Y86突变与氯喹耐药性（CQR）联系起来的报道。携带Pfcrt K76和Pfmdr-1 N86等位基因（野生/野生（WW））以及单突变Pfmdr-1 Y86（WM）的分离株具有最低的IC50几何平均值（GMIC50），而携带Pfcrt T76/Pfmdr-1 Y86等位基因（突变/突变（MM））以及单突变Pfcrt T76（MW）的分离株具有最高值。在治疗前样本中，存在强烈的连锁不平衡，MM和WW过多，单突变体（MW和WM）不足，这表明前者的寄生虫适应性较高，后者较低。
