颗粒物和CD4<sup>+</sup>T淋巴细胞IFN-γDNA甲基化在儿童变应性鼻炎发病中的机制研究

李幼瑾; 李牛; 牟喆; 马蓓颖; 江帆; 陈洁

doi:10.13201/j.issn.1001-1781.2016.07.004

颗粒物和CD4⁺T淋巴细胞IFN-γDNA甲基化在儿童变应性鼻炎发病中的机制研究

- 1. 上海交通大学医学院附属上海儿童医学中心耳鼻咽喉科(上海, 200127);
- 2. 上海交通大学医学院附属上海儿童医学中心儿童转化医学研究所;
- 3. 上海市浦东新区气象局;
- 4. 环境与儿童健康-教育部重点实验室上海交通大学医学院附属上海儿童医学中心儿童行为发育科
基金项目:
国家自然科学基金资助项目（No：81502815）；上海市科研技术委员会科研计划项目（No：15ZR1427000）；浦东新区科技发展基金创新资金（No：PKJ2014-Y01）；上海交通大学医学院科技基金项目（No：14XJ22007）

详细信息

通讯作者: 陈洁,E-mail:13611715123@163.com

中图分类号: R765.21

收稿日期: 2015-12-10

The study of atmospheric particulate matters and IFN-γDNA methylation in CD4⁺T cells from patients with AR children

- 1. Department of Otorhinolaryngology, Shanghai Children's Medical Center Affiliated with Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China;
- 2. Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine;
- 3. Shanghai Meteorological Bureau;
- 4. Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center Affiliated with Shanghai Jiaotong University School of Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health

More Information

Corresponding author: CHEN Jie, E-mail: 13611715123@163.com

Received Date: 10 December 2015

摘要

摘要: 目的：探讨大气污染环境对AR儿童CD4⁺TIFN-γ基因启动子区域甲基化的表观遗传调控及相关转录水平表达的影响。方法：对35例6~12岁确诊为持续性AR患儿进行随访，收集患儿血样及设立匹配30例为正常对照组，均进行IFN-γ基因启动子区域的甲基化克隆测序并使用实时定量逆转录聚合酶链反应检测其mRNA表达水平。根据上海市环境局提供的PM₁₀和PM_2.5数据，结合居住地址和气象监测点经纬度资料，利用克里格插值法，同时使用上海地区颗粒物穿透率系数模型和儿童室内外活动时间的调查，对PM_2.5和PM₁₀的个人综合暴露评估。结果：AR组CD4⁺T淋巴细胞中IFN-γ基因启动子区域平均甲基化水平明显高于对照组（P<0.05）；其中位点-299、+119、+168甲基化程度有差异（P=0.004，P=0.029，P=0.035）；AR组IFN-γ转录水平明显降低（P<0.05），并与其平均DNA甲基化水平呈负性相关（r=-0.341，P<0.01）。校正后AR患儿长期暴露的颗粒物PM_2.5浓度与其IFN-γ基因启动子区域甲基化程度呈正相关（β=1.441，SD=0.672，P<0.05）。结论：AR患儿IFN-γ基因启动子区域甲基化高水平可能受到PM_2.5的影响。
- 儿童 /
- 鼻炎,变应性 /
- 颗粒物 /
- IFN-γ基因甲基化 /
- Th2亚群细胞极化
Abstract: Objective: To investigate the possible effects of meteorological and environmental factors on AR of children and IFN-γgene specific DNA methylation levels in CD4⁺ T cells of patients with AR.Method: Undergoing follow-up on 35 pediatric AR patients(6-12 years).Data on daily sulfur dioxide(SO₂),nitrogen dioxide(NO₂),particulate matter of diameter smaller than 10 micrometer(PM₁₀)and particulate matter of diameter smaller than 2.5 micrometer(PM_2.5),the average of ozone(O₃) per 8 hours was available as average values derived from the data of 6 state-controlled monitoring stations distributed across Pudong district,Shanghai. We quantified IFN-γ (interferon-γ)gene specific DNA methylation levels in CD4⁺ T cells from 35 patients with AR and 30 healthy controls. mRNA levels of IFN-γ gene were measured by real-time reverse transcriptase-PCR. Methods of personal exposure assessment of PM_2.5 and PM₁₀ were measured.Result: Compared with control, IFN-γ promoter region was hypermethylated in AR CD4⁺T cells (P<0.05). Of all observed CpG sites in IFN-γ promoter region, there were significant differences in CpG^-299, CpG⁺¹¹⁹,CpG⁺¹⁶⁸(P=0.004,P=0.029,P=0.035). IFN-γ mRNA expression was significantly increase in CD4⁺T cells (P<0.05). The level of IFN-γ mRNA expression was negatively correlated to mean level of methylation in IFN-γ promoter region.After adjusting, level of long exposure PM_2.5 was positively correlated with level of methylation in IFN-γ promoter region.Conclusion: Level of methylation in IFN-γ promoter region may be affected by long exposure PM_2.5.
- children /
- rhinitis allergic /
- particulate matter /
- IFN-γgene methlyation /
- polarity of Th2

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