摘要
目的研究中缅边境地区恶性疟原虫4个与抗疟药抗性相关基因的多态性,并与该地区以往检测结果进行比较,了解和分析该地区恶性疟原虫药物抗性新趋势。方法应用巢氏PCR或普通PCR方法检测中缅边境地区2014年恶性疟现症病人血样中恶性疟原虫4个抗药相关基因点突变情况,并与2007-2009年检测结果进行比较分析。结果该地区的恶性疟原虫DHFR基因51,59,108和164位点氨基酸有不同程度突变,其中三突变NRNL型为28.1%,IRNI型为10.0%,四突变IRNL型为61.9%,未见野生型和双突变。对PfDHPS的436,437,540和581位点的突变情况进行分析,仅见三突变,突变频率分别为SGEG型14.4%,SGNG型35.6%,AGEA型50.0%。对PfMDR1的86和1246位点进行分析,仅有86位点突变,频率为32%。未见1246位点突变。对PfATPase6分子的多态性分析显示全部为野生型,未见突变型。结论中缅边境地区恶性疟原虫抗性相关基因多态性与以往年比较有变化,其中DHFR、MDR1基因突变率升高,可为该地区恶性疟的防治提供参考。
Objectives To study polymorphisms in antimalarial resistance genes, such as the dihydrofolate reductase thymidylate synthase gene （PfDHFR）, dihydropteroate synthase （PfDHPS）, multidrug resistance 1 （PfMDR1）, and calcium ATPase6 （PfATP6）, of Plasmodium falciparum from the Sino-Myanmar border and to compare findings with previous data from the same region in order to ascertain changes and to examine possible trends. Methods Primarily nested PCR and PCR were used to examine polymorphisms in antimalarial resistance genes in P. falciparum patients from the Sino-Myanmar border. Results There are various mutations at position 51, 59, 108, and 164 within the PfDHFR gene, including triple mutations and quadruple mutations. The haplotype NRNL was noted at a frequency of 28.1%, IR- NI was noted at a frequency of 10.0%, and IRNL was noted at a frequency of 61.9%. Four SNPs - S436A, A437G, K540E/N, and A581G - were detected in PfDHPS, though only triple mutations were noted. The haplotype SGEG was noted at a frequency of 14.4%, SGNG was noted at a frequency of 35.6%, and AGEA was noted at a frequency of 50.0%. Only 1 mutation at position 86 was noted in PfMDR1, and its frequency was 32%. No mutation was noted in PfATP6. Conclusion Polymorphisms in antimalarial resistance genes of P. falciparum from the Sino-Myanmar border have changed somewhat from the previous data, and this finding may provide important clues to the use of antimalarials.
出处
《中国病原生物学杂志》
CSCD
北大核心
2016年第12期1086-1088,共3页
Journal of Pathogen Biology
基金
国家自然科学基金面上项目(No.81371844)
重庆市自然科学基金面上项目(No.cstc2013jcyjA10113)
关键词
疟原虫
恶性
抗性基因
多态性
Plasmodium falciparum
resistance genes
polymorphism
