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调节性T细胞信号通路中关键基因单核苷酸多态性与变应性鼻炎免疫治疗疗效的相关性研究

ISSN号：1673-0860
期刊名称：《中华耳鼻咽喉头颈外科杂志》
时间：0
分类：R394[医药卫生—医学遗传学;医药卫生—基础医学]
作者机构：[1]首都医科大学附属北京同仁医院耳鼻咽喉头颈外科北京市耳鼻咽喉科研究所鼻病研究北京市重点实验室,100730, [2]首都医科大学附属北京同仁医院过敏科
相关基金：国家自然科学基金重大国际合作项目（81420108009）;国家杰出青年基金（81025007）;长江学者和创新团队（IRT13082）;科技部“十二五”国家科技支撑计划课题（2014BA107804）;国家自然科学基金青年项目（30973282、81100706）;国家自然科学基金应急管理项目（81441031）;国家自然科学基金面上项目（81570895）;北京市医管局重点医学专业发展计划（ZYLX201310）

关键词：鼻炎, 变应性, 单核苷酸多态性, 免疫治疗, Rhinitis, allergic , Single nucleotide polymorphism , Immunotherapy

中文摘要：

目的探讨调节性T细胞（Tregulatorycells，Treg）通路中涉及的关键基因单核苷酸多态性（single-nucleotidepolymorphisms，SNP）与变应性鼻炎（allergicrhinitis，AR）特异性免疫治疗（specificimmunetherapy，SIT）疗效的遗传相关性模式。方法2012年1月至12月，以中国北京地区居住的接受标准化特异性免疫治疗的单纯尘螨过敏的AR患者102例为研究对象（来源于北京同仁医院过敏科门诊），在免疫治疗前及治疗1年后分别对研究对象进行鼻部症状评分、鼻腔体征评分以及日常生活总体困扰评分三项指标的检测以评估疗效，根据Hapmap网站提供的中国北京地区人群覆盖FOXP3、IL．2、TGF—B以及EB134个候选基因范围及上下游各1000kb的标签SNP信息，选取覆盖以上4个候选基因的代表性标签SNP位点共43个，在MassARRAY实验平台完成SNP位点的基因型检测，以Plink软件进行统计学分析。结果根据SIT疗效评估三项指标进行遗传相关性的分层分析，鼻部症状中喷嚏的改善与IL-2基因的m77468365位点以及FOXP3基因的rs2280883、rs2232365、rs3761548位点的多态性相关。流涕症状的改善与IL-2基因的m77468365位点以及FOXP3基因的rs2280883、rs2232365、rs3761548位点的多态性相关。鼻塞症状的改善与TGF-B基因的rs747857、rs6508975、rs2241715、rs12462166、rs12983775、m1800470、rs2317130位点以及FOXP3基因的rs2280883、m2232365、rs3761548位点的多态性相关。鼻痒症状的改善与FOXP3基因的m2280883、rs2232365、rs3761548位点的多态性有关。而鼻部症状的整体改善程度与IL-2基因的rs77468365位点以及FOXP3基因的rs2280883、rs2232365、rs3761548位点的多态性相关。鼻部体征中下鼻甲黏膜肿胀程度的改善与EB13基因的rs670188位点以及FOXP3基因的m2280883、m2232365、rs3761549、rs3761548、rs3761547位点的多态性相关。下鼻甲黏膜色泽的改善与IL-2基因的rs77468365位点，EBl3基因的rs39358

英文摘要：

Objective To investigate the genetic association pattern between single-nucleotide polymorphisms （SNP） of key genes in T regulatory cells signaling pathways and the efficacy of allergic rhinitis （AR） specific immune therapy（SIT）. Methods A population of 102 AR patients（ Beijing Tongren hospital, from January to Decemeber 2012 ） caused by simple dust mite received standardized specific immune therapy, who lived in Beijing region was recruited. In immunotherapy before and after 1 years of treatment, the study objects were scored by nasal symptoms score, nasal signs score and total score of daily life distress three indicators to assess the efficacy. A total of 43 reprehensive marker SNP which were in FOXP3,IL-2, TGF-13and EBD gene regions and the upstream and downstream 1 000 kb were selected according to the Beijing people database from Hapmap website. The individual genotyping was performed by MassARRAY platform. Plink software was used for statistic analysis. Results Subgroup analysis for the efficacy evaluation of three indicators displayed that IL-2_rs77468365, FOXP3 （ rs2280883, rs2232365 and rs3761548） were associated with the improvement of sneezing in nasal symptoms. IL-2_rs77468365, FOXP3 （rs2280883, rs2232365 and rs3761548） were associated with the improvement of runny nose in nasal symptoms. TGF-13 （ rs747857, rs6508975, rs2241715, rs12462166, rs12983775, rs1800470 and rs2317130） and FOXP3 （rs2280883, rs2232365 and rs3761548 ） were associated with the improvement of nasal obstruction in nasal symptoms. FOXP3 （rs2280883, rs2232365 and rs3761548 ）were associated with the improvement of nasal itching in nasal symptoms. IL-2_rs77468365 and FOXP3 （ rs2280883, rs2232365 and rs3761548） were associated with the overall improvement in nasal symptoms. EBI3_rs670188 and FOXP3 （rs2280883, rs2232365, rs3761549, rs3761548 and rs3761547） were associated with the improvement of inferior turbinate mueosa swelling in nasal signs. IL-2 rs77468365, EBI3_rs393581, TGF-13 （rs1146

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