Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Faculty of Medicine, King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand.
Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Infect Genet Evol. 2018 Oct;64:168-177. doi: 10.1016/j.meegid.2018.06.027. Epub 2018 Jun 21.
Plasmodium vivax resistance to chloroquine (CQ) was first reported over 60 years ago. Here we analyzed sequence variations in the multidrug resistance 1 gene (Pvmdr1), a putative molecular marker for P. vivax CQ resistance, in field isolates collected from three sites in Thailand during 2013-2016. Several single nucleotide polymorphisms previously implicated in reduced CQ sensitivity were found. These genetic variations encode amino acids in the two nucleotide-binding domains as well as the transmembrane domains of the protein. The high level of genetic diversity of Pvmdr1 provides insights into the evolutionary history of this gene. Specifically, there was little evidence of positive selection at amino acid F1076L in global isolates to be promoted as a possible marker for CQ resistance. Population genetic analysis clearly divided the parasites into eastern and western populations, which is consistent with their geographical separation by the central malaria-free area of Thailand. With CQ-primaquine remaining as the frontline treatment for vivax malaria in all regions of Thailand, such a population subdivision could be shaped and affected by the current drugs for P. falciparum since mixed P. falciparum/P. vivax infections often occur in this region.
恶性疟原虫对氯喹（CQ）的耐药性早在 60 多年前就有报道。本研究分析了 2013-2016 年在泰国三个地点采集的现场分离株中多药耐药 1 基因（Pvmdr1）的序列变异，该基因被认为是恶性疟原虫对 CQ 耐药的一个潜在分子标志物。研究发现了先前与 CQ 敏感性降低相关的几个单核苷酸多态性。这些遗传变异编码了蛋白中两个核苷酸结合结构域和跨膜结构域的氨基酸。Pvmdr1 的高度遗传多样性为该基因的进化历史提供了线索。具体来说，在全球分离株中，F1076L 氨基酸的正选择证据很少，这表明其不太可能作为 CQ 耐药的一个可能标志物。种群遗传分析清楚地将寄生虫分为东部和西部种群，这与泰国中部无疟疾区的地理隔离相一致。由于 CQ-伯氨喹啉仍然是泰国所有地区间日疟的一线治疗药物，这种种群细分可能会受到当前治疗恶性疟原虫药物的影响，因为该地区经常出现混合感染恶性疟原虫和间日疟原虫的情况。
