新疆维吾尔自治区妇女宫颈感染人乳头瘤病毒16型E4和L2的遗传变异分析

Genetic variation analysis of Human Papillomavirus 16 E4 and L2 in women with cervical infection in Xinjiang Uygur Autonomous Region

目的探讨人乳头瘤病毒16(HPV16)E4、L2基因变异及氨基酸变化,分析HPV16的进化特征。方法从医院收集40例HPV16感染阳性的宫颈脱落细胞样本和40例宫颈组织细胞样本,提取样本的病毒DNA,对40例宫颈脱落细胞的DNA进行HPV16 E4和L2 Sanger测序及对40例宫颈组织细胞DNA高通量测序,构建HPV16 E4和L2基因系统进化树,分析HPV16 E4和L2基因的变异特征。结果有72个HPV16 E4变异样本,10个核苷酸变异位点(4种错义变异和7种同义变异),74个HPV16 L2变异样本,40个核苷酸变异位点(23种错义变异和18种同义变异)。宫颈癌(CC)中T4177C、A4288C、A4654C变异频率明显高于非宫颈癌,差异有统计学意义(P<0.05)。结论①新疆维吾尔自治区主要流行病毒株为欧洲株,少数为亚洲株。②HPV16 L2基因中T4177C、A4288C、A4654C在宫颈癌中的变异频率高于非宫颈癌,且G4181A与亚洲株相关。

Objective To explore the nucleotide variation and protein amino acid changes of E4 and L2 genes of Human Papillomavirus 16(HPV16),and to analyze the evolutionary characteristics of HPV16 virus.Methods 40 HPV16 infection-positive cervical exfoliated cells samples and tissue cell samples were collected from hospital,viral DNA was extracted,Sanger sequencing perform in cervical exfoliated cells DNA and high-throughput sequencing technology sequenced in cervical tissues DNA for E4 and L2 genes of HPV16,HPV16 E4 and L2 gene phylogenetic evolution trees were constructed,and variation of HPV16 E4 and L2 genes were analyzed.Results There were 72 HPV16 E4 variant samples with nucleotide variants(4 missense mutations and 7 synonymous mutations)at 10 sites,HPV16 L2 gene variants in 74 samples,and nucleotide variants(23 missense mutations and 18 synonymous mutations)at 40 sites.The variation frequency of T4177C,A4288C and A4654C in cervical cancer was significantly higher than that in non-cervical cancer,and the difference was statistically significant(P<0.05).Conclusion①The main HPV16 virus strains in Xinjiang are European strains,and a few are Asian strains.②The mutation frequency of T4177C,A4288C and A4654C in HPV16 L2 gene is higher than that in non-cervical cancer,and G4181A is related to the Asian strain.