Toll样受体7 rs179016多态性对转录活性的影响

高帆; 周义新; 吴梦平; 谢超楠; 张云; 朱萍; 岳明

doi:10.16462/j.cnki.zhjbkz.2016.05.012

Toll样受体7 rs179016多态性对转录活性的影响

doi: 10.16462/j.cnki.zhjbkz.2016.05.012

高帆¹,
周义新²,
吴梦平³,
谢超楠³,
张云^3,4, ,,
朱萍⁵,
岳明⁶

1. 沈阳军区第202医院医务处, 辽宁沈阳 110003;
2. 沈阳军区疾病预防控制中心疫情信息科, 辽宁沈阳 110034;
3. 南京医科大学公共卫生学院流行病与卫生统计学系, 江苏南京 210029;
4. 南京军区军事医学研究所流行病与微生物研究所, 江苏南京 210002;
5. 南京医科大学第一附属医院医务处, 江苏南京 210029;
6. 南京医科大学第一附属医院感染病科, 江苏南京 210029

基金项目:

国家自然科学基金（81273146,81502853）；江苏省自然科学基金（BK20151026）

详细信息

作者简介:
高帆(1982-),女,山东济南人,主治医师,学士。主要研究方向:疾病预防控制。

中图分类号: R512.63;R349.6
计量
- 文章访问数: 191
- HTML全文浏览量: 22
- PDF下载量: 33
- 被引次数: 0
出版历程
- 收稿日期: 2015-12-26
- 修回日期: 2016-03-20

The influence of the polymorphism of toll like receptor 7 rs179016 on the transcriptional activity

1. Medical Department, the 202 Hospital, Shenyang Military Command, Shenyang 110003, China;
2. Epidemic Information Section, Center for Disease Control and Prevention of Shenyang Military Command, Shenyang 110034, China;
3. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China;
4. Institute of Epidemiology and Microbiology, Military Medical Institute of Nanjing Military Command, Nanjing 210002, China;
5. Department of Medical Affairs, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;
6. Department of Infectious Diseases, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

摘要

摘要: 目的 Toll样受体7（toll like receptor 7,TLR7）在识别和介导抗丙型肝炎病毒（hepatitis C virus,HCV）免疫应答中有重要作用。本研究旨在分析TLR7 rs179016单核苷酸多态性对TLR7基因转录活性的影响。方法收集22例健康男性者血液，提取全基因组DNA及外周血单个核细胞，采用实时定量逆转录-聚合酶链反应（reverse transcription-polymerase chain reaction,RT-PCR）法检测TLR7 mRNA水平，并采用荧光素酶报告基因法，检测含有rs179016 C、G等位基因的质粒及空白质粒的HEK-293T细胞在培养24 h后荧光素强度，分析该位点对TLR7转录活性的影响。结果携带rs179016危险等位基因C组TLR7 mRNA表达水平低于rs179016G组（t=-7.352，P<0.001），转染含有rs179016G质粒的细胞表达较高强度的荧光素酶活性。结论 TLR7 rs179016多态性可能通过影响TLR7基因的转录和表达水平来影响该受体功能的发挥，可能与HCV的易感性和感染转归有关。
- Toll样受体 /
- 多态性,单核苷酸 /
- 肝炎,丙型,慢性
Abstract: Objective Toll like receptor 7 (TLR7) plays an important role in sensing and provoking an immune response in hepatitis C virus (HCV) infection. This study aims to investigate the correlation of the polymorphism of TLR7 rs179016 with the transcription activity of TLR7. Methods 22 male volunteers were included in this study. The TLR7 mRNA expression was evaluated by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). The expression of the cultured HEK-293T cell lysates containing rs179016 C/G or empty plasmid was assessed using a dual-luciferase reporter gene system and compared. Results A lower TLR7 mRNA level was observed in subjects carrying G genotype than those carrying C genotype (t=-7.352,P<0.001). The fluorescence intensity of cells containing rs179016G was stronger than that of cells containing rs179016C. Conclusions Our data indicated that TLR7 rs179016 C genotype was associated with the lower transcription and translation of TLR7, which may contribute to an increased susceptibility to HCV infection.
- Toll-like receptor /
- Polymorphism,single nucleotide /
- Hepatitis C,chronic

HTML全文

参考文献(15)

Chattergoon MA, Levine JS, Latanich R, et al. High plasma interleukin-18 levels mark the acute phase of hepatitis C virus infection [J]. J Infect Dis, 2011,204(11):1730-1740.

Negro F, Alberti A. The global health burden of hepatitis C virus infection [J]. Liver Int, 2011,31(Suppl 2):1-3.

吴梦平,谢超楠,岳明,等. 血浆25羟基维生素D水平及其受体基因多态性与慢性丙型肝炎易感性的相关性研究 [J]. 中华疾病控制杂志, 2015,19(11):1083-1086.

Howell J, Angus P, Gow P, et al. Toll-like receptors in hepatitis C infection: implications for pathogenesis and treatment [J]. J Gastroen Hepatol, 2013,28(5):766-776.

Uematsu S, Akira S. Toll-like receptors and type I interferons [J]. J Biol Chem, 2007,282(21):15319-15323.

Horsmans Y, Berg T, Desager JP, et al. Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection [J]. Hepatology, 2005, 42(3):724-731.

Lee J, Wu CC, Lee KJ, et al. Activation of anti-hepatitis C virus responses via Toll-like receptor 7 [J]. Proc Natl Acad Sci USA, 2006,103(6):1828-1833.

Wei XS, Wei CD, Tong YQ, et al. Single nucleotide polymorphisms of toll-like receptor 7 and toll-like receptor 9 in hepatitis C virus infection patients from central China [J]. Yonsei Med J, 2014,55(2):428-434.

Netea MG, Wijmenga C, O'Neill LA. Genetic variation in Toll-like receptors and disease susceptibility [J]. Nat Immunol, 2012,18(13):535-542.

Wang CH, Eng HL, Lin KH, et al. TLR7 and TLR8 gene variations and susceptibility to hepatitis C virus infection [J]. PLoS One, 2011,6(10):226-235.

Schott E, Witt H, Neumann k, et al. A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV infection [J]. J Hepatol, 2007,47(2):203-211.

Xue XX, Gong JM, Tang SD, et al. Single nucleotide polymorphisms of toll-like receptor 7 in hepatitis C virus infection patients from a high-risk Chinese population [J]. Inflammation, 2014,38(1):142-151

薛兴欣,蔡立,王佳佳,等. 有偿献血人群血浆IL-18水平与HCV感染及其基因型的相关性研究 [J]. 中华疾病控制杂志, 2014,18(7):590-593.

赵莉,王国玮,王振海. HCV感染小鼠小胶质细胞后TLR7 mRNA和IL-6表达 [J]. 中国神经免疫学和神经病学杂志, 2011,18(3):178-181.

Deng Y, Zhao J, Sakurai D, et al. MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus [J]. PLoS Genetics, 2013,9(2):e1003336.

施引文献

资源附件(0)

访问统计