National Institute of Malaria Research (Indian Council of Medical Research), Sector - 8, Dwarka, New Delhi 110 077, India.
National Institute of Malaria Research (Indian Council of Medical Research), Sector - 8, Dwarka, New Delhi 110 077, India.
Acta Trop. 2020 Feb;202:105095. doi: 10.1016/j.actatropica.2019.105095. Epub 2019 Jul 16.
Plasmodium falciparum sarcoplasmic reticulum Ca ATPase (PfSERCA) is sarcoplasmic reticulum membrane bound transporter to regulate cytosol Ca ions. Ca act as secondary messenger and play important role in differentiation of parasite during its life cycle. Present study is epidemiological surveillance of PfSERCA (Pf3D7_0106300) gene fragment harboring 263, 402, 431 codon to look for its single nucleotide polymorphism which is well documented to be associated with Artemisinin tolerance. Filter paper with finger pricked blood samples for Plasmodium falciparum infected uncomplicated malaria patients were obtained for region as diverse as down the longitude from east to west of India i.e. Mizoram, Tripura, Meghalaya, Jharkhand, Odhisa. There observed no mutation for codon 263 at all study sites. Mizoram showed highest PfSERCA diversity with well known SNPs of L402 V, E431 K, A438 V and novel mutations as well i.e. A338 V, S357Y, S379Y. Tripura reported highest proportion of Plasmodium isolates (18.5%) with E431 K single nucleotide polymorphism. Moving towards the west i.e. Meghalaya, Jharkhand, Odhisa showed no occurrence of most prevalent PfSERCA 431, 402 polymorphism worldwide but some novel mutations and its haplotypes. In present study, significantly increased proportion of novel PfSERCA polymorphism among children suggests the susceptibility of these Plasmodium falciparum strains to acquired immunity. Mizoram, sharing open international border with south east asia, demonstrated highest PfSERCA diversity. Spatial PfSERCA diversity from far north east India to moving towards west implies its association with antimalarial susceptibility.
恶性疟原虫肌浆网 Ca2+-ATP 酶（PfSERCA）是肌浆网膜结合转运蛋白，可调节细胞质中的 Ca2+离子。Ca2+作为第二信使，在寄生虫生命周期中的分化中发挥重要作用。本研究对 PfSERCA（Pf3D7_0106300）基因片段进行了流行病学监测，该基因片段包含 263、402、431 个密码子，寻找其单核苷酸多态性，已有充分的文献证明其与青蒿素耐药性有关。从印度东部到西部，包括米佐拉姆邦、特里普拉邦、梅加拉亚邦、恰尔康得邦和奥里萨邦等不同地区采集了感染无并发症疟疾的患者的指血滤纸样本。在所有研究地点，都没有观察到密码子 263 发生突变。米佐拉姆邦的 PfSERCA 多样性最高，存在众所周知的 L402V、E431K、A438V 以及 novel mutations 等 SNP，还有 A338V、S357Y、S379Y 等突变。特里普拉邦报告称，E431K 单核苷酸多态性的疟原虫分离株比例最高（18.5%）。往西走，即梅加拉亚邦、恰尔康得邦和奥里萨邦，没有出现全球最常见的 PfSERCA 431、402 多态性，但出现了一些 novel mutations 及其 haplotypes。在本研究中，儿童中新 PfSERCA 多态性的比例显著增加，表明这些恶性疟原虫株对获得性免疫的敏感性增加。与东南亚接壤的米佐拉姆邦表现出最高的 PfSERCA 多样性。从印度东北部到西部的 PfSERCA 空间多样性暗示了其与抗疟敏感性的关联。
