中国麻风菌株系统发生生物地理学与麻风传播

Phylogeography of M. leprae Strain and the Spread of Leprosy in China

目的了解我国麻风菌基因型特征及其在国内的传播情况,为控制麻风传播提供有效信息。方法采用SNP分型与17个位点的VNTR分型,对目前国内尚有麻风新发病例的17个省及西藏、新疆自治区的190例麻风患者的菌株进行分型。结果除SNP外,18-8,12-5,rpoT,(TA)10等VNTR位点是鉴别我国麻风菌株的重要标记物。目前的菌株分型揭示中国存在四个不同基因型的麻风菌群和不同地域水平的聚类株。东南部的福建、广东及邻近省的SNP1型菌株与它们特有的VNTR基因型关联;东南地区的SNP3型菌株可通过VNTR分型,与我国其他地区的SNP3菌株区分开;东部的江苏、安徽、以及与西藏接壤的四川藏区发现了在日本、韩国检测到的rpoT4拷贝的SNP3型菌株。云南丘北、贵州兴义与分散的四川菌株存在基因多态性,但麻风流行区具有当地特有的聚类株。结论 VNTR与SNP结合分型揭示陆上/北向丝绸之路为中国麻风病传播路径外,还有经南海和东海的"海上丝绸之路"传播路径。VNTR分型是揭示具有民族和地理多样性的中国麻风菌株基因型的有力工具。其分型为各级水平上的病例发现和追踪传播奠定了基础。

Objective To understand the genotypes and transmission of M. leprae in China and to provide valuable in- formation to interrupt the transmission of leprosy. Methods Molecular strain typing based on seventeen var- iable number of tandem repeats （VNTRs） loci and SNP had been applied to the investigation of 190 patients spanning seventeen provinces and two autonomous regions Xinjiang and Tibet where leprosy still could be de- tected. Results Besides SNP,the VNTR loci of 18-8,12-5,rpoT, （TA） 10 were important markers to dis- tinguish Chinese M. leprae strains. The current strain typing revealed the presence of four different leprosy strains with different genotypes and several scenarios of clustering of leprosy. The novel VNTR linked strains were of SNP type 1 in Guangdong, Fujian and Guangxi, southeastern China. A subset of VNTR distinguish- able strains of type 3 co-exist in this southeastern region. Type 3 strains with rpoT VNTR allele of 4, detec- ted in Japan and Korea were discovered in Jiangsu and Anhui in the east and in Sichuan bordering Tibet. The strains from leprosy endemic areas of Qiubei Yunnan, Xingyi Guizhou, and across Sichuan had genetic diversity, and further analysis revealed local distinct clusters. Conclusion The results of VNTR and SNP genotyping reveal that the Northern route of transmission via the Silk Road, the historic maritime routes in the South and East China Sea are involved in the spread of leprosy within and out of China. VNTR analysis is a useful tool in uncovering characteristic patterns across the multiethnic and divergent geographic landscape of China, which provides a basis for case finding and tracking of leprosy at various administrative levels.