Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy.

Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy.
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DOI:
10.1186/1475-2875-9-355
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发表时间:
2010-12-08
期刊:
影响因子:
3
通讯作者:
Ferreira-da-Cruz Mde F
Ferreira-da-Cruz Mde F
中科院分区:
医学3区
文献类型:
--
作者:
Gama BE;de Oliveira NK;de Souza JM;Santos F;de Carvalho LJ;Melo YF;Rosenthal PJ;Daniel-Ribeiro CT;Ferreira-da-Cruz Mde F

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本研究的目的是更好地了解巴西引进ACT前pfatpase 6和pfmdr 1基因已知多态性的遗传多样性,以获得恶性疟原虫寄生虫的基因型快照,可用作未来研究的基线参考。对2002年、2004年和2006-2007年采集的恶性疟原虫样本进行基因分型,使用PCR和DNA测序,在pfmdr 1基因密码子86、130、184、1034、1042、1109和1246,以及243、263、402、431、623、630、639、683、716,776、769和771。pfmdr 1单倍型NEF/CDVY被发现在97%的样品。在pfatpase 6的情况下,检测到四种单倍型,野生型(37%),630 S(35%),402 V(5%)和双突变630 S + 402 V(23%)。虽然pfmdr 1和pfatpase 6中的一些多态性得到了验证,但在巴西引入该疗法之前,未检测到可能介导ACT反应改变的两个基因的单倍型。因此,本文所述的单倍型可以非常有用地作为没有ACT药物压力的恶性疟原虫群体的基线参考。
This study was performed to better understand the genetic diversity of known polymorphisms in pfatpase6 and pfmdr1 genes before the introduction of ACT in Brazil, in order to get a genotypic snapshot of Plasmodium falciparum parasites that may be used as baseline reference for future studies. Parasites from P. falciparum samples collected in 2002, 2004 and 2006-2007 were genotyped using PCR and DNA sequencing at codons 86, 130, 184, 1034, 1042, 1109 and 1246 for pfmdr1 gene, and 243, 263, 402, 431, 623, 630, 639, 683, 716, 776, 769 and 771 for pfatpase6 gene. A pfmdr1 haplotype NEF/CDVY was found in 97% of the samples. In the case of pfatpase6, four haplotypes, wild-type (37%), 630 S (35%), 402 V (5%) and double-mutant 630 S + 402 V (23%), were detected. Although some polymorphism in pfmdr1 and pfatpase6 were verified, no reported haplotypes in both genes that may mediate altered response to ACT was detected before the introduction of this therapy in Brazil. Thus, the haplotypes herein described can be very useful as a baseline reference of P. falciparum populations without ACT drug pressure.
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