Genetic variations of E6 and long control region of human papillomavirus type 16 from patients with cervical lesion in Liaoning, China.
Genetic variations of E6 and long control region of human papillomavirus type 16 from patients with cervical lesion in Liaoning, China.
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辽宁地区宫颈病变患者人乳头瘤病毒16型E6和长控制区基因变异
DOI：
10.1186/1471-2407-13-459
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发表时间：
2013-10-07
期刊：
影响因子：
3.8
通讯作者：
Ruan Q
中科院分区：
文献类型：
--
作者：
Sun Z;Lu Z;Liu J;Wang G;Zhou W;Yang L;Liu C;Wang B;Ruan Q
高危型人乳头瘤病毒16型（HPV 16）是宫颈癌的危险因素。以前的研究表明，E6基因或HPV 16长控制区（LCR）的多态性可能会改变病毒的致癌潜力。本研究旨在探讨中国人群HPV 16 E6基因和LCR的遗传变异及其与患者病情的关系。收集东北地区304例HPV 16阳性宫颈管标本。PCR-测序分析E6基因和LCR序列。种群中存在两个谱系，即EUR谱系和As谱系。基于HPV 16原型，E6基因最常见的变异是T178 A/G（48.7%），其次是G94 A（12.2%）和T350 G（9.9%）突变。E6氨基酸变异发生率依次为D25 E（46.3%）、L 83 V（9.9%）和H78 Y（4.3%）。304株HPV 16阳性宫颈标本中均发现LCR变异。最常观察到的LCR变异是过渡替换G7193 T、7434 CIns、G7521 A和7863 ADel（100%）。As谱系与HPV持续感染和疾病状态≥ CIN 2，3相关。EUR谱系变异体显示与≥ CIN的严重程度呈负相关趋势2，3。在LCR的41个变异中，25个（61.0%）位于转录因子的结合位点。经年龄校正后，≥ CIN 2，3的发生与E6基因R10 G/L 83 V突变和LCR基因C7294 T共变异显著相关。本研究发现，As谱系与HPV持续感染、疾病状态≥ CIN 2，3之间存在相关性，EUR谱系与≥ CIN 2，3严重程度呈负相关趋势之间存在相关性。在中国女性HPV 16感染人群中发现E6区R10 G/L 83 V和LCR区C7294 T共变异与CIN-2，3发生风险增加相关。这些发现表明HPV 16多态性影响CIN-2，3的发展。
High-risk human papillomavirus type 16 (HPV16) is a risk factor for cervical cancer. Previous studies suggest that polymorphisms in the E6 gene or the long control region(LCR)of HPV16 may alter the oncogenic potential of the virus. The aims of this study were to investigate the genetic variations of HPV16 E6 gene and LCR in isolates from Chinese population and correlation of the E6 and LCR polymorphisms with disease status of infected patients. HPV16 positive endocervical specimens were collected from 304 women living in Northeast of China. Sequences of E6 gene and LCR were analyzed by PCR-sequencing. Two lineages were found in the populations, including EUR lineage and As lineage. Based on the HPV16 prototype, the most frequent variation in the E6 gene was T178A/G (48.7%), followed by mutations of G94A (12.2%) and T350G (9.9%). The rank orders of incidence of E6 variations in amino acid were as follows: D25E (46.3%), L83V (9.9%) and H78Y (4.3%). Nucleotide variations in LCR were found in all the 304 isolates from HPV16 positive cervical samples. The most commonly observed LCR variations were the transition replacement G7193T, 7434CIns, G7521A and 7863ADel (100%). The As lineage was associated with HPV persistent infections and with disease status of ≥CIN2,3. The EUR lineage variants showed a negative trend of association with the severity of ≥CIN2,3. Among 41 variations found in LCR, 25 (61.0%) were located at the binding sites for transcription factors. Occurrence of ≥CIN2,3 was significantly associated with the mutations of R10G/L83V in E6 and the C7294T co-variation in LCR, after adjusting for ages of infected patients. Associations between As lineage and HPV persistent infections, and with disease status of ≥CIN2,3, and an association between the EUR lineage and negative trend of association with the severity of ≥CIN2,3 were found in this study. An association between a co-variation of R10G/L83V in E6 and C7294T in LCR and an increased risk for developing CIN-2,3 was found in a HPV16 infected population of Chinese women. These findings indicate that HPV16 polymorphism influences development of CIN-2,3.
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