Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins
Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins
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DOI：
10.1016/j.parint.2007.12.004
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发表时间：
2008-06-01
影响因子：
1.9
通讯作者：
Severini, Carlo
中科院分区：
文献类型：
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作者：
Menegon, Michela;Sannella, Anna Rosa;Severini, Carlo
应用部分DNA序列测定方法，对来自意大利16个疟疾流行区的75株输入性恶性疟原虫PfATP酶6基因多态性进行了研究。总体而言，大多数分离株（62.7%）显示野生型基因型。在14株（18.6%）菌株中发现了431位（E→K）的单核苷酸多态性（SNP），而在243位（H→Y）和623位（A→E）的多态性仅发现了一次。序列分析还发现了以前未发现的以下非同义多态性的存在：L402 V（n=12），K771 E（n=3），A630 S（n=1），N683 K（n=1）和K776 N（n=1）。在28株具有多态性的分离株中，24株为单核苷酸多态性，仅4株为双或三核苷酸多态性（塞内加尔402 V/623 E，安哥拉431 K/630 S，中国431 K/776 N，尼日尔402 V/431 K/771 E）。本研究仅关注PfATPase 6多态性，因此，结果不支持或否定所观察到的基因多态性是青蒿素耐药的基础的假设，也没有被药物治疗选择。
75Plasmodium falciparumisolates from imported malaria cases in Italy originating from 16 malaria endemic areas were investigated forPfATPase6polymorphism by partial DNA sequencing. Overall, the majority of isolates (62.7%) displayed a wild-type genotype. A previously known single nucleotide polymorphism (SNP) at position 431(E→K) was observed in 14 isolates (18.6%), whereas the polymorphisms at codons 243(H→Y) and 623(A→E) were detected only once. Sequence analysis also revealed the presence of the following non-synonymous polymorphisms not previously identified: L402V (n=12), K771E (n=3), A630S (n=1), N683K (n=1) and K776N (n=1). Of the 28 isolates showing polymorphism, 24 carried single SNP and only 4 displayed double or triple SNPs (402V/623E genotype in Senegal, 431K/630S in Angola, 431K/776N in China, and 402V/431K/771E in Niger). This study focused only onPfATPase6polymorphism, thus the results do not support or invalidate the hypothesis that the observed gene polymorphism underlies resistance to artemisinins, nor has been selected by drug treatment.