新型间日疟原虫红细胞结合蛋白在中国中部及周边国家边境地区的遗传多样性研究

GENETIC DIVERSITY OF NOVEL PLASMODIUM VIVAX ERYTHROCYTE BINDING PROTEIN IN CENTRAL CHINA AND BORDER AREAS OF NEIGHBORING COUNTRIES

为分析新型间日疟原虫红细胞结合蛋白(PvEBP)在中国中部地区(安徽)及周边国家边境地区(缅甸和越南)的遗传多样性和种群分布特征,提取31例中国(安徽)和22例缅甸(Laiza镇)间日疟原虫患者基因组DNA,经PCR扩增并测序,同时从GenBank中分别获取缅甸和越南地区相应基因序列共34例,进行PvEBP基因多态性和遗传分化分析。结果显示PvEBP核苷酸多态性和单倍型多样性在我国中部地区安徽较低(π=0.00051,Hd=0.634),在缅甸和越南地区相对较高;三个流行区分离株中PvEBP-RII受到正向选择压力的影响(dN/dS>1),突变集中在PvEBP-RII;不同群体间PvEBP基因的遗传分化程度较高;三个群体共享单倍体型较少,仅单倍型Hap_4同时出现在三个不同流行区。结果表明,中国(安徽)和周边国家(缅甸和越南)分离株PvEBP的基因多态性及分化程度因地理隔离差异较大,PvEBP-RII可作为间日疟原虫红内期候选疫苗的重要靶点。

To comprehend the genetic diversity and population distribution characteristics of the novel Plasmodium vivax erythrocyte binding protein(PvEBP)in central China(Anhui)and border areas of Myanmar and Vietnam,the genomic DNA of P.vivax patients from China(Anhui)(n=31)and Myanmar(Laiza town)(n=22)were extracted,amplified by PCR and sequenced.The corresponding sequences of 34 samples in Myanmar and Vietnam were obtained from GenBank to analyze the polymorphism and genetic differentiation of PvEBP gene.The results showed that nucleotide polymorphism and haplotype diversity of PvEBP gene were relatively low in central China(Anhui),whereas they were relatively high in Myanmar and Vietnam.The PvEBP-RII in isolates from three endemic areas were under positive selection,and the mutations were concentrated in PvEBP-RII.The degree of genetic differentiation of PvEBP gene among three populations was much high(P<0.05).There were obvious geographic differences of PvEBP gene in three endemic regions.Three populations shared fewer haplotypes,only Hap_4 existed in three different endemic areas.The results showed that the genetic polymorphisms and differention degree of PvEBP in isolates from China(Anhui)and neighboring countries(Myanmar and Vietnam)were quite different due to geographical isolation,PvEBP-RII can be used as an important target for the candidate vaccine of P.vivax in the blood-stage.