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墨西哥女性中58型人乳头瘤病毒E6和E7癌基因的遗传变异性

Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in Mexican Women.

作者信息

Conde-Ferraez Laura, Pacheco-Arjona Ramón, Novelo Canul Cinthia, Gomez-Carballo Jesus, Ramirez-Prado Jorge Humberto, Ayora-Talavera Guadalupe, González-Losa Maria Del Refugio

机构信息

Universidad Autónoma de Yucatán, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Laboratorio de Virología, Mérida, Mexico.

Consejo Nacional de Ciencia y Tecnología-Universidad Autónoma de Yucatán, Facultad de Medicina Veterinaria y Zootecnia, Mérida, Mexico.

出版信息

Intervirology. 2017;60(6):235-246. doi: 10.1159/000489306. Epub 2018 Jun 26.

DOI:10.1159/000489306
PMID:29945151
Abstract

BACKGROUND/AIMS: The study aimed to describe human papillomavirus (HPV) 58 genetic variability in E6 and E7 oncogenes from women in southeast Mexico and their phylogenetic relationships with the sequences from other geographical regions.

METHODS

The E6-E7 region was amplified by nested PCR, and sequenced for identification of polymorphisms, phylogenetic trees construction, and haplotype and fixation tests.

RESULTS

HPV58 positive samples were obtained from a repository, 54 were amplified, 47 sequences for the E6 gene, and 51 sequences for the E7 gene were obtained. Fifteen new E6 mutations were found; the most frequent were G279T (G57V; 29.78%), T249G (F47C; 34.04%), and A270G (Y54C; 34.04%), and previously reported c307t (63.82%). For E7, 17 known mutations were found, the most frequent were C632T (T20I), 35.30%, G760A (G63S), 35.30%, and t744g 74.50%. No significant association with the severity of the lesions was found. The polytomy in the E6 tree did not allow proposing phylogenetic relationship, and E7 tree presented defined branches. All sequences were presumably A lineage, most closely related to A1 and/or A3 sublineage. HPV58 variants are not specific for a geographical area. Population and fixation analyses suggest a possible Asian origin of HPV58 from Yucatan. The most frequent E7 haplotype in Yucatan groups with other populations of the world.

CONCLUSION

The genetic variability of HPV58 from Mexico was described for the first time. E7 was more conserved than E6. New mutants present exclusively in Yucatan were identified.

摘要

背景/目的:本研究旨在描述墨西哥东南部女性人乳头瘤病毒(HPV)58型E6和E7致癌基因的遗传变异性,以及它们与其他地理区域序列的系统发育关系。

方法

通过巢式PCR扩增E6-E7区域,并进行测序以鉴定多态性、构建系统发育树以及进行单倍型和固定性测试。

结果

从储存库中获取HPV58阳性样本,54个样本被扩增,获得了47个E6基因序列和51个E7基因序列。发现了15个新的E6突变;最常见的是G279T(G57V;29.78%)、T249G(F47C;34.04%)和A270G(Y54C;34.04%),以及先前报道的c307t(63.82%)。对于E7,发现了17个已知突变,最常见的是C632T(T20I),35.30%,G760A(G63S),35.30%,以及t744g 74.50%。未发现与病变严重程度有显著关联。E6树中的多歧现象不允许提出系统发育关系,而E7树呈现出明确的分支。所有序列可能属于A谱系,与A1和/或A3亚谱系关系最为密切。HPV58变体并非特定于某个地理区域。群体和固定性分析表明,尤卡坦半岛的HPV58可能起源于亚洲。尤卡坦半岛最常见的E7单倍型与世界其他人群的单倍型相同。

结论

首次描述了墨西哥HPV58的遗传变异性。E7比E6更保守。鉴定出了仅存在于尤卡坦半岛的新突变体。

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