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伊朗南部霍尔木兹甘省二氢叶酸还原酶和二氢蝶酸合酶基因中的氨基酸突变

Amino acid mutation in dihydrofolate reductase and dihydropteroate synthetase genes in Hormozgan Province, southern Iran.

作者信息

Maghsoodloorad Somayeh, Hosseinzadeh Nahid, Haghighi Ali, Solgi Rahmat, Yusuf Mustapha Ahmed, Hatam Gholamreza

机构信息

Department of Parasitology and Mycology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Vector Borne Dis. 2019 Apr-Jun;56(2):170-173. doi: 10.4103/0972-9062.263716.

DOI:10.4103/0972-9062.263716
PMID:31397394
Abstract

Molecular analysis of antifolate resistance-associated genes-dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) of Plasmodium vivax is important in predicting the emergence of drug resistance to sulphadoxine-pyrimethamine (SP). The present study aimed to determine the polymorphism of dhfr and dhps genes in P. vivax field isolates. Samples from 80 microscopically diagnosed vivax malaria cases were collected from endemic areas of malaria in Hormozgan Province of Iran, from June 2010 to November 2015. The two sets of codons at position 33, 57, 58, 117, 173 of dhfr and 382, 383, and 553 of dhps genes were analysed by direct sequencing of PCR products. The majority of the isolates (70%) harboured a wild-type allele for P. vivax dhfr (Pvdhfr) and P. vivax dhps (Pvdhps). Mutations were detected in three codons of Pvdhfr (P33L, S58R and S117N) and single codon in Pvdhps (A383G). Novel mutations that have not been identified previously at codon 459 (D459A) of Pvdhps were also observed. The high prevalence of point mutation as well as the rising triple mutation of Pvdhfr and Pvdhps genotypes necessitate change in programmes and guidelines to eliminate P. vivax in future.

摘要

间日疟原虫抗叶酸相关基因——二氢叶酸还原酶(dhfr)和二氢蝶酸合酶(dhps)的分子分析对于预测磺胺多辛-乙胺嘧啶(SP)耐药性的出现很重要。本研究旨在确定间日疟原虫野外分离株中dhfr和dhps基因的多态性。2010年6月至2015年11月,从伊朗霍尔木兹甘省疟疾流行地区收集了80例经显微镜诊断为间日疟的病例样本。通过对PCR产物进行直接测序,分析了dhfr基因第33、57、58、117、173位以及dhps基因第382、383和553位的两组密码子。大多数分离株(70%)携带间日疟原虫dhfr(Pvdhfr)和间日疟原虫dhps(Pvdhps)的野生型等位基因。在Pvdhfr的三个密码子(P33L、S58R和S117N)和Pvdhps的一个密码子(A383G)中检测到突变。还观察到Pvdhps第459位密码子(D459A)此前未发现的新突变。点突变的高流行率以及Pvdhfr和Pvdhps基因型三重突变的增加,使得未来消除间日疟原虫的计划和指南有必要做出改变。

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