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

摘要

对缅甸境内恶性疟病例的PfKelch13基因突变与青蒿素耐药的关联性及PfKelch13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PfKelch13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PfKelch13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PfKelch13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PfKelch13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PfKelch13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 ob-tained 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 artemisi-nin 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 Plas-modium falciparum population in Yunnan.