输入性恶性疟原虫Pfcrt和pfmdr1基因突变关联性分析  

Correlation analysis on mutations of chloroquine resistant transporter and multi-drug resistance 1 gene in Plasmodium falciparum imported to Wuhan, China

作　　者：周水茂[1] 李联军 贾西帅 杨燕[1] 徐明星[1] 陈芳[1] ZHOU Shui-mao;LI Lian-jun;JIA Xi-shuai;YANG Yan;XU Ming-xing;CHEN Fang(Wuhan Center for Disease Control and Prevention, Wuhan 430015, Hubei Province, China;Hubei Huangmei Dahe Center Hospital)

机构地区：[1]武汉市疾病预防控制中心病原生物检验所,武汉430015 [2]湖北省黄梅大河中心医院,湖北黄冈435500

出　　处：《中国媒介生物学及控制杂志》2018年第3期242-245,共4页Chinese Journal of Vector Biology and Control

摘　　要：目的了解输入性恶性疟原虫氯喹抗性转运蛋白基因(Pfcrt)和恶性疟原虫多药抗性基因1(pfmdr1)相关位点突变情况及其关联性。方法 2009-2016年,采集武汉市从非洲和东南亚等回国人员恶性疟患者血样,利用巢式PCR扩增恶性疟原虫Pfcrt和pfmdr1基因,分别用限制性内切酶ApoⅠ、AseⅠ和EcoRv对产物进行酶切,分析相关位点的突变性。结果 232例输入性恶性疟患者Pfcrt76和pfmdr186、1042、1246位点的突变率分别为55.2%、17.2%、5.2%和8.6%,pfmdr1总突变率为26.3%;东南亚患者血样未检出pfmdr186和pfmdr11246位点突变;非洲输入性恶性疟患者Pfcrt76突变和未突变中pfmdr186、1042、1246位点及pfmdr1总突变率分别为28.6%、3.8%、12.4%、36.2%和10.4%、2.1%、7.3%、17.7%。患者症状与Pfcrt76、pfmdr186、1042、1246位点突变连锁不平衡分析,D′和r^2分别为0.230和0.018、0.290和0.004、0.996和0.012、0.150和0.035。结论输入地为非洲和东南亚缅甸的恶性疟原虫pfmdr1基因突变位点存在差异,Pfcrt76突变与pfmdr1突变和pfmdr186点突变呈正相关。Objective To identify Plasmodium falciparum chloroquine resistant transporter（Pfcrt） point mutations and P. falciparum multidrug resistance 1（pfmdr1） and their correlation in imported P. falciparum. Methods Blood samples were collected from returnees infected with P. falciparum in endemic areas of Africa and Southeast Asia during 2009-2016 in W uhan city. The Pfcrt76 gene and pfmdrl gene were amplified by nested PCR, and the products were digested by restriction endonuclease Apo I, Ase I and EcoRv. The mutation rate was analyzed. Results A total of 232 patients with falciparum malaria were involved in the study. The mutation rates for Pfcrt76, pfmdrl loci 86, 1042, and 1246 were 55.2%,17.2%, 5.2%, and 8.6% respectively, the total mutation rate for pfmdrl was 26.3%. The mutation rates for pfmdr1 loci 86,1042, 1246 and pfmdr1 were 28.6%, 3.8%, 12.4%, and 36.2%, respectively in the samples with mutation in Pfcrt76, but10.4%, 2.1%, 7.3%, and 17.7%, respectively in the samples without mutation in Pfcrt76 from Africa. The linkage disequilibrium analysis between symptoms and the mutations of Pfcrt76, pfmdr186, 1042, and 1246 were conducted, and the value of D＇ and r^2 were 0.230 and 0.018, 0.290 and 0.004, 0.996 and 0.012, 0.150 and 0.035, respectively, for each mutation. Conclusion The pfmdrl mutation sites between Africa and Southeast Asia have statistically significant differences. Pfcrt76 was positively correlated with pfmdrl mutation and pfmdr186 point mutation.

关 键 词：输入病例 恶性疟原虫 恶性疟原虫氯喹抗性转运蛋白基因 恶性疟原虫多药抗性基因1 基因突变 

分 类 号：R382.31[医药卫生—医学寄生虫学]