A shared Asian origin of the triple-mutant dhfr allele in Plasmodium falciparum from sites across Africa
A shared Asian origin of the triple-mutant dhfr allele in Plasmodium falciparum from sites across Africa
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DOI：
10.1086/518512
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发表时间：
2007-07-01
影响因子：
6.4
通讯作者：
Clain, Jerome
中科院分区：
文献类型：
--
作者：
Maiga, Oumou;Djimde, Abdoulaye A.;Clain, Jerome
背景磺胺嘧啶-乙胺嘧啶作为无并发症恶性疟原虫疟疾的一线治疗和整个撒哈拉以南非洲地区妊娠期间歇性预防性治疗的有效性受到与乙胺嘧啶耐药性相关的dhfr等位基因传播的影响。最近在4个非洲国家报道了与N51 I + C59 R + S108 N三重突变dhfr等位基因相关的主要单倍型。一个更全面的图片在非洲的这种突变等位基因的演变是缺乏。从11个非洲国家选择了75个携带野生型dhfr等位基因的恶性疟原虫分离株和204个携带三重突变dhfr等位基因的恶性疟原虫分离株。利用与dhfr基因紧密连锁的4个微卫星标记对携带这些等位基因的染色体进行遗传多样性分析。在204株携带dhfr等位基因的分离株中，有175株（85%）具有与泰国分离株相同的单倍型。其余3个突变株和1个dhfr等位基因4个突变株（N51 I + C59 R + S108 N + I164 L）的单倍型均与优势单倍型密切相关。携带祖先三重突变dhfr等位基因的寄生虫的迁移驱动整个西非和中非与乙胺嘧啶抗性相关的dhfr等位基因的传播。
Background. Usefulness of sulfadoxine-pyrimethamine as first-line therapy for uncomplicated Plasmodium falciparum malaria and intermittent preventive treatment in pregnancy throughout sub-Saharan Africa is compromised by the spread of dhfr alleles associated with pyrimethamine resistance. A predominant haplotype associated with the N51I+C59R+S108N triple-mutant dhfr allele has been reported recently in 4 African countries. A more comprehensive picture of the evolution of this mutant allele in Africa is lacking.Methods. Seventy-five P. falciparum isolates carrying the wild-type dhfr allele and 204 carrying the triple-mutant dhfr allele from 11 African countries were selected. The genetic diversity of the chromosomes bearing these alleles was analyzed with 4 microsatellite markers closely linked to the dhfr gene.Results. Seventy-three different 4-locus haplotypes carrying the wild-type dhfr allele were found. By contrast, 175 ( 85%) of 204 isolates carrying the triple-mutant dhfr allele shared a unique haplotype, identical to the one identified in Thailand. For the remaining triple-mutant isolates and one isolate with the quadruple-mutant dhfr allele ( N51I+C59R+S108N+I164L), haplotypes were closely related to the predominant haplotype by mutation or recombination.Conclusions. Migration of parasites carrying an ancestral triple-mutant dhfr allele drives the spread of dhfr alleles associated with pyrimethamine resistance throughout West and Central Africa.