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泰国疟疾流行地区间日疟原虫二氢叶酸还原酶(DHFR)和二氢蝶酸合成酶(DHPS)氨基酸突变的地理分布

Geographical distribution of amino acid mutations in Plasmodium vivax DHFR and DHPS from malaria endemic areas of Thailand.

作者信息

Rungsihirunrat Kanchana, Sibley Carol Hopkins, Mungthin Mathirut, Na-Bangchang Kesara

机构信息

Faculty of Allied Health Sciences, Thammasat University, Pathumtani, Thailand.

出版信息

Am J Trop Med Hyg. 2008 Mar;78(3):462-7.

PMID:18337344
Abstract

Both malaria treatment and prophylaxis target the parasite dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes. Specific point mutations in these genes confer resistance to sulfadoxine-pyrimethamine (SP) in both Plasmodium falciparum and P. vivax. We used direct sequencing to examine the prevalence of point mutations in pvdhps and pvdhfr in 160 P. vivax isolates collected from areas along the international borders of Thailand. Results show that the majority of the isolates harbored a quadruple mutant allele of pvdhfr and a double mutant allele of pvdhps, but the distribution was not uniform. The highly mutant allele combination was especially prevalent along the Thai-Myanmar border, whereas the majority of the isolates from areas along the Thai-Cambodian and Thai-Malaysian borders carried double mutant alleles of pvdhfr and single mutant alleles of pvdhps. Novel mutations that have not been identified previously at codon 512 of pvdhps (K512M, K512E, K512T) were also found.

摘要

疟疾治疗和预防均针对疟原虫的二氢蝶酸合酶(DHPS)和二氢叶酸还原酶(DHFR)这两种酶。这些基因中的特定点突变使恶性疟原虫和间日疟原虫对磺胺多辛-乙胺嘧啶(SP)产生耐药性。我们采用直接测序法检测了从泰国国际边境沿线地区收集的160株间日疟原虫分离株中pvdhps和pvdhfr点突变的流行情况。结果显示,大多数分离株携带pvdhfr的四重突变等位基因和pvdhps的双重突变等位基因,但分布并不均匀。高度突变的等位基因组合在泰缅边境尤为普遍,而来自泰柬边境和泰马边境沿线地区的大多数分离株携带pvdhfr的双重突变等位基因和pvdhps的单一突变等位基因。还发现了pvdhps第512密码子(K512M、K512E、K512T)之前未被鉴定的新突变。

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