Sharma Jitendra, Dutta Prafulla, Khan S A, Soni Monika, Mahanta Jagadish
Entomology and Filariasis Division, Regional Medical Research Centre (ICMR), North East Region, Dibrugarh, India.
J Vector Borne Dis. 2014 Dec;51(4):282-5.
BACKGROUND & OBJECTIVES: Resistance against partner drugs of artemisinin has been reported from different parts of India. The study aims to find out the single nucleotide polymorphisms in Plasmodium falciparum ATPase6 gene associated with artemisinin resistance.
Blood samples were collected from 141 patients with P. falciparum monoinfection in malaria endemic zones of Assam and Arunachal Pradesh. A 645 bp portion of PfATPase6 gene was amplified and sequenced to determine the frequency of mutations associated with resistance to artemisinin.
Mutations at codon S769N, which have been proposed to confer artemisinin resistance, were not detected in our study samples. Instead of that a novel non-synonymous mutation (C-T) at 1847 bp position resulting in serine to phenylalanine alteration at codon S616F was detected from the P. falciparum field isolates in Changlang district of Arunachal Pradesh, whereas no mutation was detected in any of the analyzed samples in Assam indicating that wild type PfATPase6 genotype was found circulating in this region. Overall, based on the mutational pattern, two haplotypes of PfATPase6 gene were observed during the study, the wild type and mutant S616F allele. The overall haplotype diversity (Hd) was found to be: 0.069 and nucleotide diversity (per site Pi): 0.00012. Highest haplotype diversity was recorded in Changlang district of Arunachal Pradesh having Hd value of 0.33333 along with single polymorphic site and nucleotide diversity (Pi): 0.00060. A pair-wise fixation index (FST) value of 0.16667 indicates great genetic differentiation within the parasite population of Changlang district with the population of Karbi Anglong, Chirang, Tinsukia, Sivasagar, Jorhat, NC Hills, Lakhimpur, Golaghat and Dibrugarh districts of Assam and Lohit district of Arunachal Pradesh.
INTERPRETATION & CONCLUSION: A better understanding of the distribution of antimalarial drug resistance with malaria parasite may provide insight into some of the epidemiological determinants of the increasing case burden.
印度不同地区已报告对青蒿素联合用药产生耐药性。本研究旨在找出恶性疟原虫ATP酶6（PfATPase6）基因中与青蒿素耐药性相关的单核苷酸多态性。
从阿萨姆邦和阿鲁纳恰尔邦疟疾流行区的141例恶性疟原虫单一感染患者采集血样。扩增并测序PfATPase6基因的645 bp片段，以确定与青蒿素耐药性相关的突变频率。
在我们的研究样本中未检测到已被提出可赋予青蒿素耐药性的第769位密码子S769N突变。相反，从阿鲁纳恰尔邦昌朗地区的恶性疟原虫野外分离株中检测到一个新的非同义突变（C-T），位于1847 bp位置，导致第616位密码子丝氨酸变为苯丙氨酸（S616F），而在阿萨姆邦分析的任何样本中均未检测到突变，表明该地区存在野生型PfATPase6基因型。总体而言，根据突变模式，研究期间观察到PfATPase6基因的两种单倍型，即野生型和突变型S616F等位基因。单倍型多样性（Hd）总体为0.069，核苷酸多样性（每位点Pi）为0.00012。阿鲁纳恰尔邦昌朗地区记录到最高的单倍型多样性，Hd值为0.33333，伴有一个多态性位点，核苷酸多样性（Pi）为0.00060。成对固定指数（FST）值为0.16667，表明昌朗地区的疟原虫群体与阿萨姆邦的卡尔比安隆、奇朗、廷苏基亚、锡瓦萨加尔、乔哈特、北恰查尔山区、拉克希普尔、戈拉哈特和迪布鲁格尔地区以及阿鲁纳恰尔邦的洛希特地区的群体之间存在很大的遗传分化。
更好地了解疟原虫对抗疟药物的耐药性分布，可能有助于深入了解病例负担增加的一些流行病学决定因素。
