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[中国湖北地区HPV16 E6和E7基因的基因变异研究及系统发育分析]

[The study of gene variation and phylogenetic analysis of HPV16 E6 and E7 gene in Hubei, China].

作者信息

Ding Xiao-hua, Zhang Fan, Cai Hong-bin, Yang Zhang-qiu

机构信息

Virology Institute of Medical College, Wuhan University, Hubei 430071, China.

出版信息

Bing Du Xue Bao. 2010 Sep;26(5):368-72.

PMID:21043136
Abstract

To study the gene variation and the distribution of HPV16 variant in Hubei, China, DNA was extracted from cervical cancer tissue samples. The E6 and E7 genes of HPV16 were amplified and the PCR products were sequenced using E6- and E7-specific primers. Fortyseven cases were found mutations at nucleotide position 178 of HPV16 E6 gene in 80 cervical cancer samples. This mutation resulted in amino acid change from Asp to Glu. The rate of mutation at nucleotide position 178 of E6 gene was 58. 75%. Twenty two cases were found mutations at nucleotide position 647 of HPV16 E7 gene in 31 cervical cancer samples. This mutation resulted in amino acid change from Asn to Ser. The rate of mutation was 70.97%. These results showed that mutations at nucleotide position 178 of E6 gene, nucleotide position 647 of E7 gene of HPV16 in cerveical cancer samples were prevalent in Hubei, China. Phylogenetic analysis showed that Asian (As) variants of HPV16 are predominated in Hubei, China. European (Ep) varinats were also found in Samples in Hubei areas. None of Asian American (AA), African-1 (Af-1), African-2 (Af-2) variants of HPV16 was found in this region. Whether Asian (As) variants of HPV16 are more oncogenic and play a much more important role in the progress of cervical cancer than European (Ep) variants is not clear. More sequences of E6 and E7 gene in CIN and normal cervical tissue samples and study of the function of E6 and E7 protein of these HPV16 variants are needed to adress above question.

摘要

为研究中国湖北地区人乳头瘤病毒16型(HPV16)的基因变异及变异株分布情况,从宫颈癌组织样本中提取DNA。采用E6和E7特异性引物对HPV16的E6和E7基因进行扩增,并对PCR产物进行测序。在80例宫颈癌样本中,47例在HPV16 E6基因第178位核苷酸处发生突变,该突变导致氨基酸由天冬氨酸变为谷氨酸,E6基因第178位核苷酸的突变率为58.75%。在31例宫颈癌样本中,22例在HPV16 E7基因第647位核苷酸处发生突变,该突变导致氨基酸由天冬酰胺变为丝氨酸,突变率为70.97%。这些结果表明,中国湖北地区宫颈癌样本中HPV16的E6基因第178位核苷酸、E7基因第647位核苷酸的突变较为普遍。系统发育分析表明,中国湖北地区HPV16以亚洲(As)变异株为主,同时也发现了欧洲(Ep)变异株,未发现HPV16的亚美(AA)、非洲-1(Af-1)、非洲-2(Af-2)变异株。HPV16亚洲(As)变异株是否比欧洲(Ep)变异株更具致癌性,在宫颈癌进展中发挥更重要作用尚不清楚。需要对更多宫颈上皮内瘤变(CIN)和正常宫颈组织样本中的E6和E7基因序列进行检测,并研究这些HPV16变异株E6和E7蛋白的功能,以解决上述问题。

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