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中国宫颈上皮内瘤变2级和3级女性中的人乳头瘤病毒16型E6基因突变与p53密码子72多态性

HPV16 E6 mutations and p53 codon72 polymorphism among women with cervical intraepithelial neoplasia 2 and 3 in China.

作者信息

Piao J, You K, Guo Y, Zhang Y, Li Z, Geng L

出版信息

Eur J Gynaecol Oncol. 2016;37(5):649-652.

Abstract

OBJECTIVE

To study the distribution of HPV16 E6 gene mutations and p53 codon72 polymorphism among women with HPV16+ cervical precancerous lesions and explore their relationship with the risk of cervical intraepithelial neoplasia (CIN) 2, 3. Materials and Meth- ods: This study analyzed a total of 112 cases of exfoliated HPV16+ cervical cell specimens which were divided into group I (normal and CIN1, 55 cases) and group2 (CIN2, 3, 57 cases). Among the 112 specimens, 85 cases were successfully amplified for HPV E6 gene by PCR and the PCR products were sequenced directly. P53 codon72 region was also amplified from the 112 specimens and the PCR products were sequenced directly and compared with the standard sequence.

RESULTS

Among the 85 amplified HPV sequences, point mutations such as T178G, T350G, G132A, A442C, T310G, G94T, C551A, etc. were found, among which, T178G showed the highest rate (51.76%). The rate of HPV16 E6 mutation T178G in CIN2, 3 group was significantly higher than that in normal and CINI group, i.e., in the 112 amplified p53 codon72 sequences, the distribution of Pro/Pro genotype in normal, and CIN1 group was significantly different from that in CIN2, 3 groups, and the disease risk of Pro/Pro genotype was much higher than that of Arg/Arg and Arg/Pro genotypes.

CONCLUSION

HPV16 E6 T178G mutation increases the disease risk of CIN2, 3. Meanwhile, compared with Arg/Arg and Arg/Pro genotypes, p53 codon72 Pro/Pro genotype more associated with the disease risk of CIN2, 3.

摘要

目的

研究HPV16 E6基因突变和p53密码子72多态性在HPV16阳性宫颈上皮内瘤变女性中的分布情况,并探讨它们与宫颈上皮内瘤变(CIN)2、3级风险的关系。材料与方法:本研究共分析了112例HPV16阳性宫颈脱落细胞标本,分为I组(正常及CIN1级,55例)和II组(CIN2、3级,57例)。在这112份标本中,85例通过PCR成功扩增出HPV E6基因,PCR产物直接测序。同时从112份标本中扩增p53密码子72区域,PCR产物直接测序并与标准序列比较。

结果

在85条扩增出的HPV序列中,发现了T178G、T350G、G132A、A442C、T310G、G94T、C55A等点突变,其中T178G突变率最高(51.76%)。CIN2、3级组中HPV16 E6基因T178G突变率显著高于正常及CIN1级组。在112条扩增出的p53密码子72序列中,正常及CIN1级组中Pro/Pro基因型的分布与CIN2、3级组有显著差异,且Pro/Pro基因型的患病风险远高于Arg/Arg和Arg/Pro基因型。

结论

HPV16 E6基因T178G突变增加了CIN2、3级的患病风险。同时,与Arg/Arg和Arg/Pro基因型相比,p53密码子72 Pro/Pro基因型与CIN2、3级的患病风险更相关。

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