云南省疟疾报告病例恶性疟原虫PfKelch13基因突变与青蒿素耐药性的关联性分析  

The correlation analysis between PfKelch13 gene mutation of Plasmodium falciparum isolates and artemisinin resistance in Yunnan Province

作　　者：孙艾明 王剑[2] 董莹[2] 陈梦妮[2] 徐艳春[2] 邓艳[2] 毛祥华[2] SUN Ai-ming;WANG Jian;DONG Ying;CHEN Meng-ni;XU Yan-chun;DENG Yan;MAO Xiang-hua(Puer Section,Institute of Pathogenic and Vectors,Dali University,Puer 665000;Yunnan Center of Malaria Research;Yunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research,Puer 665000,China)

机构地区：[1]大理大学病原与媒介生物研究所普洱分部,普洱665000 [2]云南省寄生虫病防治所云南省疟疾研究中心云南省虫媒传染病防控研究重点实验室,普洱665000

出　　处：《生物学杂志》2018年第1期21-25,共5页Journal of Biology

基　　金：国家自然科学基金国际(地区)合作与交流项目(No.81220108019);国家自然科学基金地区科学基金项目(No.81660559);云南省科技项目应用基础研究计划青年项目(No.Y0120150295)

摘　　要：对缅甸境内恶性疟病例的Pf Kelch13基因突变与青蒿素耐药的关联性及Pf Kelch13基因在种群间的分化差异进行了分析。结果表明云南省疟疾报告病例Pf Kelch13基因序列中,单倍型共有13种,He为0.0481,错义突变序列占34.7%(66/190),F446I的突变率最高,为25.3%(48/190);缅甸境内病例基因序列中,单倍型共有19种,He为0.0440,错义突变序列占58.8%(114/194),F446I的突变率最高,为43.3%(84/194),云南恶性疟种群Pf Kelch13基因kelch结构域遗传多样性相对较高,两个种群的遗传分化指数Fst=0.0410(P<0.05),群体内、群体间的变异分别占95.90%和4.10%,以缅甸境内病例推算的青蒿素耐药性产生与Pf Kelch13基因kelch结构域446位点突变的OR值为1.640(95%CI:1.284~2.095),与12种位点突变的OR值为1.840(95%CI:1.412~2.398)。研究结果表明,云南省疟疾报告病例与缅甸境内病例的恶性疟原虫分离株种群在Pf Kelch13基因kelch结构域上的分化程度低,以缅甸病例分离株推算出的Pf Kelch13基因突变与青蒿素耐药性产生的遗传关联程度适用于云南报告病例的恶性疟原虫种群。In this paper,we analyed the correlation between PfKelch13 gene mutation and artemisinin resistance and the differentiation of PfKelch13 gene among populationsin in Myanmar.The results showed that in 190 DNA sequences of kelech domain in PfKelch13 gene from Yunnan blood samples had 13 haplotypes,the expected heterozygosity(He)was 0.0449 and the nonsynonymous mutations sequences accounted for 34.7%(66/190),the F446I mutation rate was the highest with 25.3%(48/190);19 haplotypes were obtained from 194 DNA sequences from Myanmar bloods samples,the expected heterozygosity(He)was 0.0449 and the nonsynonymous mutations sequences accounted for 58.8%(114/194),and F446I mutation rate was the highest with 43.3%(84/194);the genetic diversity of PfKelch13 gene in kelch domain of Plasmodium falciparum population in Yunnan Province was relatively high,the index of genetic differentiation of two populations was 0.0410(Fst=0.0410,P<0.05),and the variation within the population and amomg the populations accounted for 95.90%and 4.10%respectively.The expected heterozygosity(He)of the OR value between artemisinin resistance and haplotypes was 0.0449 and the nonsynonymous mutations sequences accounted PfKelch13 gene kelch domain at 446 site mutation was 1.640(95%CI:1.284~2.095)and the OR value of the 12 site mutations was 1.840(95%CI:1.412-2.398).Therefore,the differentiation degree of Plasmodium falciparum in Yunnan and Myanmar was low in the PfKelch13 gene kelch domain,so the genetic association between the PfKelch13 gene mutation and artemisinin resistance in Myanmar is suitable for the report of Plasmodium falciparum population in Yunnan.

关 键 词：恶性疟病例 PfKelch13 青蒿素耐药性 关联性分析 

分 类 号：Q78[生物学—分子生物学]