HPV16 E2 gene disruption and polymorphisms of E2 and LCR: Some significant associations with cervical cancer in Indian women

HPV16 E2 gene disruption and polymorphisms of E2 and LCR: Some significant associations with cervical cancer in Indian women
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DOI:
10.1016/j.ygyno.2005.09.016
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发表时间:
2006-02-01
影响因子:
4.7
通讯作者:
Sengupta, S
Sengupta, S
中科院分区:
医学2区
文献类型:
--
作者:
Bhattacharjee, B;Sengupta, S

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目标。我们评估了一组来自印度妇女的CaCx病例(侵袭性鳞状细胞癌,n = 81)和人群对照(正常宫颈刮伤,n = 27)中HPV16分离株E2基因(破坏或完整)的状态、完整E2基因内核苷酸序列的改变和LCR。用单组引物扩增整个E2基因来检测E2的破坏,而使用重叠引物来确定是否有任何特定区域被选择性破坏。通过PCR扩增和双向测序分析E2和LCR的核苷酸变异。采用Fisher's Exact或卡方检验分析病毒因子与CaCx之间的相关性,并解释为or (95% Cl)和P值。E2破坏率在病例中较高[3.38 (1.07-10.72)];P = 0.02],在核苷酸3650和3872之间的区域(dna结合区)最大。发现欧洲(E)变异为流行亚组(病例中占87.76%,对照组中占96.30%),其余样本为亚裔美国变异。在E亚组中,E2结合位点- iv内7450位(T > C)的变异在E2未中断的病例中(21/37;56.76%)明显高于对照组(5/18;27.78%)[3.41 (1.01-11.55);P = 0.03]。除了hpv16e2中断外,E亚组未中断E2的LCR 7450T > C变异似乎是导致印度妇女CaCx发展风险的主要因素。此外,HPV16的E2基因多态性可能与疾病风险无关。(c) 2005爱思唯尔公司版权所有。
Objectives. We evaluated the status of the HPV16 E2 gene (disrupted or intact), nucleotide sequence alterations within intact E2 genes and LCR of HPV16 isolates in a group of CaCx cases (invasive squamous cell carcinomas, n = 8 1) and population controls (normal cervical scrapes, n = 27) from Indian women.Methods. E2 disruption was detected by amplifying the entire E2 gene with single set of primers, while overlapping primers were used to determine if any particular region got selectively disrupted. Nucleotide variations in E2 and LCR were analyzed by PCR amplification followed by bi-directional sequencing. The associations between the viral factors and CaCx were analyzed using Fisher's Exact or Chi-squared test and interpreted as OR (95% Cl) and P values.Results. E2 disruption was significantly higher among the cases [3.38 (1.07-10.72); P = 0.02], which was maximum in the region between nucleoticles 3650 and 3872 (DNA-binding region). The European (E) variant was found to be the prevalent subgroup (87.76% among cases and 96.30% among the controls), and the remaining samples were Asian-American variants. Among the E subgroup, variation at position 7450 (T > C) within the E2-binding site-IV was found to be significantly higher among the E2 undisrupted cases (21/37; 56.76%), compared to controls (5/18; 27.78%) [3.41 (1.01-11.55); P = 0.03].Conclusions. Besides HPV16 E2 disruption, LCR 7450T > C variation within undisrupted E2 of E subgroup appears to be a major factor contributing to the risk of CaCx development in Indian women. Furthermore, polymorphisms in the E2 gene of HPV16 may not be significant for disease risk. (c) 2005 Elsevier Inc. All rights reserved.