山东大学耳鼻喉眼学报 ›› 2019, Vol. 33 ›› Issue (3): 36-41.doi: 10.6040/j.issn.1673-3770.1.2019.021

• 研究进展 • 上一篇    下一篇

变应性鼻炎的遗传学研究现状

陆美萍1(),程雷1,2   

  1. 1. 南京医科大学第一附属医院 江苏省人民医院耳鼻咽喉科
    2. 南京医科大学国际变态反应研究中心，江苏 南京 210029
  • 收稿日期:2019-04-15 修回日期:2019-05-01 出版日期:2019-05-20 发布日期:2019-08-08
  • 通讯作者: 陆美萍 E-mail:lmp@njmu.edu.cn
  • 作者简介:陆美萍，医学博士，主任医师，副教授，硕士研究生导师。主要学术任职：中华医学会变态反应学分会青年委员，江苏省医学会变态反应学分会委员，江苏省医师协会变态反应医师分会委员，中国中西医结合学会耳鼻咽喉科专业委员会变态反应专家委员会常委，中国医师协会耳鼻咽喉科医师分会变态反应学组委员，江苏省医学会耳鼻咽喉头颈外科学分会鼻科学组副组长。曾荣获第三届全国耳鼻咽喉科医师大会“优秀青年医师奖”。主要研究领域为鼻部炎症与变态反应的遗传及分子机制，主持国家自然科学基金项目2项，发表学术论文20余篇
  • 基金资助:
    国家自然科学基金(81200747)

Current status of genetic research on allergic rhinitis

Meiping LU1(),Lei CHENG1,2   

  1. 1. Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University
    2. International Centre for Allergy Research, Nanjing Medical University, Nanjing 210029, Jiangsu, China
  • Received:2019-04-15 Revised:2019-05-01 Online:2019-05-20 Published:2019-08-08
  • Contact: Meiping LU E-mail:lmp@njmu.edu.cn

RichHTML

10

PDF (PC)

645

摘要：

变应性鼻炎是基因和环境因素共同作用导致的鼻黏膜非感染性炎症性疾病，虽然目前对其发病机制已经有了较深入的了解，对遗传因素的研究也取得了较大进展，但这些遗传相关研究结果仅限于统计学层面，与临床应用还有很大距离。对变应性鼻炎相关基因的研究策略、基因与环境的交互作用、变应性疾病基因的重叠、表观遗传修饰及基因的转化研究方向做一综述。

关键词: 变应性鼻炎, 基因, 环境, 基因-环境交互作用, 表观遗传学, 精准医学

Abstract:

Allergic rhinitis is a non-infectious inflammatory disease of the nasal mucosa caused by a combination of genetic and environmental factors. Although a fair understanding of its pathogenesis already exits and research on genetic factors associated with this condition has made significant progress, these studies are still limited to achieving statistically significant results; however, their clinical applications have a long way to go. This article mainly introduces the research strategy on genes related to allergic rhinitis, their interaction with the environment, the sharing overlap of allergic disease genes, epigenetic modifications, and the direction of gene research transformation.

Key words: Allergic rhinitis, Genes, Environment, Gene-environment interaction, Epigenetics, Precision medicine

中图分类号: 

  • R765.4
1 Brożek JL , Bousquet J , Agache I , et al . Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision[J]. J Allergy Clin Immunol, 2017,140(4): 950-958. doi:10.1016/j.jaci.2017.03.050 .
doi: 10.1016/j.jaci.2017.03.050
2 Wang XD , Zheng M , Lou HF , et al . An increased prevalence of self-reported allergic rhinitis in major Chinese cities from 2005 to 2011[J]. Allergy, 2016, 71(8): 1170-1180. doi:10.1111/all.12874 .
doi: 10.1111/all.12874
3 Sachidanandam R , Weissman D , Schmidt SC , et al . A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms[J]. Nature, 2001, 409(6822): 928-933. doi:10.1038/35057149 .
doi: 10.1038/35057149
4 Van Eerdewegh P , Little RD , Dupuis J , et al . Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness[J]. Nature, 2002, 418(6896): 426-430. doi:10.1038/nature00878 .
doi: 10.1038/nature00878
5 Ober C , Tan Z , Sun Y , et al . Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function[J]. N Engl J Med, 2008, 358(16): 1682-1691. doi:10.1056/NEJMoa0708801 .
doi: 10.1056/NEJMoa0708801
6 Allen M , Heinzmann A , Noguchi E , et al . Positional cloning of a novel gene influencing asthma from chromosome 2q14[J]. Nat Genet, 2003, 35(3): 258-263. doi:10.1038/ng1256 .
doi: 10.1038/ng1256
7 Nicolae D , Cox NJ , Lester LA , et al . Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21[J]. Am J Hum Genet, 2005, 76(2): 349-357. doi:10.1086/427763 .
doi: 10.1086/427763
8 Holloway JW , Yang IA , Holgate ST . Genetics of allergic disease[J]. J Allergy Clin Immunol, 2010, 125(2 Suppl 2): S81-S94. doi:10.1016/j.jaci.2009.10.071 .
doi: 10.1016/j.jaci.2009.10.071
9 Altshuler D , Daly MJ , Lander ES . Genetic mapping in human disease[J]. Science, 2008, 322(5903): 881-888. doi:10.1126/science.1156409 .
doi: 10.1126/science.1156409
10 McCarthy MI, Abecasis GR , Cardon LR , et al . Genome-wide association studies for complex traits: consensus, uncertainty and challenges[J]. Nat Rev Genet, 2008, 9(5): 356-369. doi:10.1038/nrg2344 .
doi: 10.1038/nrg2344
11 MacArthur J , Bowler E , Cerezo M , et al . The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)[J]. Nucleic Acids Res, 2017, 45(D1): D896-D901. doi:10.1093/nar/gkw1133 .
doi: 10.1093/nar/gkw1133
12 Li JY , Zhang Y , Zhang L . Discovering susceptibility genes for allergic rhinitis and allergy using a genome-wide association study strategy[J]. Curr Opin Allergy Clin Immunol, 2015, 15(1): 33-40. doi:10.1097/ACI.000-0000000000124 .
doi: 10.1097/ACI.000-0000000000124
13 Waage J , Standl M , Curtin JA , et al . Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis[J]. Nat Genet, 2018, 50(8): 1072-1080. doi:10.1038/s41588-018-0157-1 .
doi: 10.1038/s41588-018-0157-1
14 Huebner M , Kim DY , Ewart S , et al . Patterns of GATA3 and IL13 gene polymorphisms associated with childhood rhinitis and atopy in a birth cohort[J]. J Allergy Clin Immunol, 2008, 121(2): 408-414. doi:10.1016/j.jaci.2007.09.020 .
doi: 10.1016/j.jaci.2007.09.020
15 Holloway JW , Koppelman GH . Identifying novel genes contributing to asthma pathogenesis[J]. Curr Opin Allergy Clin Immunol, 2007, 7(1): 69-74. doi:10.1097/ACI.0b013e328013d51b .
doi: 10.1097/ACI.0b013e328013d51b
16 Yang IA , Savarimuthu S , Kim ST , et al . Gene-environmental interaction in asthma[J]. Curr Opin Allergy Clin Immunol, 2007, 7(1): 75-82. doi:10.1097/ACI.0b013 e328012ce39 .
doi: 10.1097/ACI.0b013 e328012ce39
17 London SJ , Romieu I . Gene by environment interaction in asthma[J]. Annu Rev Public Health, 2009, 30: 55-80. doi:10.1146/annurev.publhealth.031308.100151 .
doi: 10.1146/annurev.publhealth.031308.100151
18 Breton CV , Vora H , Salam MT , et al . Variation in the GST mu locus and tobacco smoke exposure as determinants of childhood lung function[J]. Am J Respir Crit Care Med, 2009, 179(7): 601-607. doi:10.1164/rccm.200809-1384OC .
doi: 10.1164/rccm.200809-1384OC
19 Palmer CN , Irvine AD , Terron-Kwiatkowski A , et al . Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis[J]. Nat Genet, 2006, 38(4): 441-446. doi:10.1038/ng1767 .
doi: 10.1038/ng1767
20 Smit LA , Siroux V , Bouzigon E , et al . CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults[J]. Am J Respir Crit Care Med, 2009, 179(5): 363-368. doi:10.1164/rccm.200810-1533OC .
doi: 10.1164/rccm.200810-1533OC
21 Chen HI , Lin YT , Jung CR , et al . Interaction between catalase gene promoter polymorphisms and indoor environmental exposure in childhood allergic rhinitis[J]. Epidemiology, 2017, 28(Suppl 1): S126-S132. doi:10.1097/EDE.0000000000000741 .
doi: 10.1097/EDE.0000000000000741
22 Rhodes HL , Thomas P , Sporik R , et al . A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status[J]. Am J Respir Crit Care Med, 2002, 165(2): 176-180. doi:10.1164/ajrccm. 165. 2.2104032 .
doi: 10.1164/ajrccm. 165. 2.2104032
23 Moffatt MF , Kabesch M , Liang LM , et al . Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma[J]. Nature, 2007, 448(7152): 470-473. doi:10.1038/nature06014 .
doi: 10.1038/nature06014
24 Tomita K , Sakashita M , Hirota T , et al . Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population[J]. Allergy, 2013, 68(1): 92-100. doi:10.1111/all.12066 .
doi: 10.1111/all.12066
25 Li XN , Howard TD , Zheng SL , et al . Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions[J]. J Allergy Clin Immunol, 2010, 125(2): 328-335.e11. doi:10.1016/j.jaci.2009.11.018 .
doi: 10.1016/j.jaci.2009.11.018
26 Kim WK , Kwon JW , Seo JH , et al . Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children[J]. J Allergy Clin Immunol, 2012, 130(2): 421-426.e5. doi:10.1016/j.jaci.2012.04.052 .
doi: 10.1016/j.jaci.2012.04.052
27 Lu MP , Chen RX , Wang ML , et al . Association study on IL4, IL13 and IL4RA polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population[J]. PLoS One, 2011, 6(11):e27363. doi： 10.1371/journal.pone.0095033 .
doi: 10.1371/journal.pone.0095033
28 Black S , Teixeira AS , Loh AX , et al . Contribution of functional variation in the IL13 gene to allergy, hay fever and asthma in the NSHD longitudinal 1946 birth cohort[J]. Allergy, 2009, 64(8): 1172-1178. doi:10.1111/j.1398-9995.2009.01988.x .
doi: 10.1111/j.1398-9995.2009.01988.x
29 Esparza-Gordillo J , Weidinger S , Folster-Holst R , et al . A common variant on chromosome 11q13 is associated with atopic dermatitis[J]. Nat Genet, 2009,41(5):596-601. doi： 10.1038/ng.347 .
doi: 10.1038/ng.347
30 Potaczek DP , Harb H , Michel S , et al . Epigenetics and allergy: from basic mechanisms to clinical applications[J]. Epigenomics, 2017, 9(4): 539-571. doi:10.2217/epi-2016-0162 .
doi: 10.2217/epi-2016-0162
31 向荣，刘昀，许昱 . FOXP3甲基化在变应性鼻炎中的作用研究[J]. 临床耳鼻咽喉头颈外科杂志,2016,30(9):707-711. doi:10.13201/j.issn.1001-1781.2016.09.009
doi: 10.13201/j.issn.1001-1781.2016.09.009
XIANG Rong , LIU Yun , XU Yu . Effect of the FOXP3 gene methylation status in pathogenesis of patients with allergic rhinitis[J]. Journal Clinical Otorhinolaryngology Head Neck Surgery(China),2016, 30(9):707-711. doi:10.13201/j.issn.1001-1781.2016.09.009
doi: 10.13201/j.issn.1001-1781.2016.09.009
32 Yang IV , Pedersen BS , Liu AH , et al . The nasal methylome and childhood atopic asthma[J]. J Allergy Clin Immunol, 2017, 139(5): 1478-1488. doi:10.1016/j.jaci. 2016.07.036 .
doi: 10.1016/j.jaci. 2016.07.036
33 Nicodemus-Johnson J , Myers RA , Sakabe NJ , et al . DNA methylation in lung cells is associated with asthma endotypes and genetic risk[J]. JCI Insight, 2016, 1(20): e90151. doi:10.1172/jci.insight.90151 .
doi: 10.1172/jci.insight.90151
34 Nestor CE , Barrenäs F , Wang H , et al . DNA methylation changes separate allergic patients from healthy controls and may reflect altered CD4+ T-cell population structure[J]. PLoS Genet, 2014, 10(1): e1004059. doi:10.1371/journal.pgen.1004059 .
doi: 10.1371/journal.pgen.1004059
35 Heffler E , Allegra A , Pioggia G , et al . MicroRNA profiling in asthma: potential biomarkers and therapeutic targets[J]. Am J Respir Cell Mol Biol, 2017, 57(6): 642-650. doi:10.1165/rcmb.2016-0231TR .
doi: 10.1165/rcmb.2016-0231TR
36 Panganiban RP , Pinkerton MH , Maru SY , et al . Differential microRNA epression in asthma and the role of miR-1248 in regulation of IL-5[J]. Am J Clin Exp Immunol, 2012, 1(2): 154-165.
37 Maes T , Cobos FA , Schleich F , et al . Asthma inflammatory phenotypes show differential microRNA expression in sputum[J]. J Allergy Clin Immunol, 2016, 137(5): 1433-1446. doi:10.1016/j.jaci.2016.02.018 .
doi: 10.1016/j.jaci.2016.02.018
38 Milger K , Götschke J , Krause L , et al . Identification of a plasma miRNA biomarker signature for allergic asthma: a translational approach[J]. Allergy, 2017, 72(12): 1962-1971. doi:10.1111/all.13205 .
doi: 10.1111/all.13205
39 Levänen B , Bhakta NR , Torregrosa Paredes P , et al . Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients[J]. J Allergy Clin Immunol, 2013, 131(3): 894-903. doi:10.1016/j.jaci. 2012. 11.039 .
doi: 10.1016/j.jaci. 2012. 11.039
40 Li YJ , Chen J , Rui XQ , et al . The association between sixteen genome-wide association studies-related allergic diseases loci and childhood allergic rhinitis in a Chinese Han population[J]. Cytokine, 2018, 111: 162-170. doi:10.1016/j.cyto.2018.08.022 .
doi: 10.1016/j.cyto.2018.08.022
41 Kersten ET , Koppelman GH . Pharmacogenetics of asthma: toward precision medicine[J]. Curr Opin Pulm Med, 2017, 23(1): 12-20. doi:10.1097/MCP.0000000000000335 .
doi: 10.1097/MCP.0000000000000335
[1] 张贵阳,黄河,冼志,张汉文,谢桂彩. 粉尘螨滴剂舌下含服免疫治疗对不同年龄段变应性鼻炎患者的临床效果评估[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 60-65.
[2] 潘晓菲,王军,肖洋,马丽晶. LncRNA CTB-147C22.8对复发性呼吸道乳头状瘤细胞侵袭的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 66-70.
[3] 刘燕,魏萍,寇巍,胡思洁,武小芳,刘萌雅,陈成,姚红兵. 儿童腺样体肥大与耳鼻咽喉科常见疾病关系的研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 149-154.
[4] 钱俊俊,周文成,吴中飞,卜冬云,汪李琴,陆美萍,程雷. 苏皖地区变应性鼻炎患者吸入性变应原谱分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 147-151.
[5] 钱方舟,黄啸博,魏钦俊,陈智斌. 致聋基因 EYA4 在斑马鱼胚胎发育中的时空表达特征分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 49-55.
[6] 田慧琴,吴中飞,陆莹,程雷. GC和CYP27B1基因多态性与汉族人群尘螨致敏的持续性变应性鼻炎的关联研究[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 71-78.
[7] 陈若希,张清照,陆美萍,朱歆洁,程雷. TLR通路基因多态性与变应性鼻炎的关联研究[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 79-87.
[8] 李华斌,赖玉婷,姜文秀. 慢性鼻窦炎的内表型研究进展及精准治疗[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 9-13.
[9] 刘冬梅,李洋,宋继科,郭大东,马先祯,毕宏生. 玻璃体切割联合硅油填充术后晶状体基因表达谱的变化及验证[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 95-98.
[10] 郭胤仕,卢慧. Ⅱ型固有淋巴细胞在变应性鼻炎发病机制中的作用[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 9-12.
[11] 邱前辉,高俊潇. 特异性免疫治疗对过敏性鼻炎和哮喘的同步控制和远期疗效[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 33-37.
[12] 秦雅楠,王琳,姜彦,闫舒,陈敏,于龙刚,李娜. 2008~2017年青岛地区变应性鼻炎常见吸入性变应原分布[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 67-72.
[13] 金兴,胡大宇,朱丽,邓芙蓉,刘俊秀. PM2.5与变应性鼻炎患者上气道阻力的相关性研究[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 77-80.
[14] 李丽莎,关凯,王子熹,崔乐. 大气污染物对于变应性鼻炎症状严重度的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 81-87.
[15] 洪海裕, 许光福, 杨烁伟,苏荣飞,黄伊厘,池梦诗,王玮豪,杨钦泰. 探究广东地区变应性鼻炎合并支气管哮喘的危险因素[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 94-98.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 林彬,王挥戈 . 功能性内镜鼻窦手术后鼻黏膜纤毛转归的研究[J]. 山东大学耳鼻喉眼学报, 2006, 20(6): 481 -487 .
[2] 张晗,黄一飞 . 抗角膜移植排斥的研究进展[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 84 -87 .
[3] 毕景云 . 鼻中隔矫正术后血肿的处理[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 90 -91 .
[4] 谢治年 综述,姬长友 审校 . RNA干扰及其在喉鳞癌研究中的应用[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 200 -203 .
[5] 白广平,李 俊,董 频 . 鼻内镜下手术治疗慢性鼻窦炎、鼻息肉180例[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 242 -243 .
[6] 李 响,徐志坚,彭解人 . 颈部异位甲状腺13例并文献复习[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 285 -285 .
[7] 明 伟,屈季宁,华清泉,詹汉章 . 显微喉镜下CO2激光治疗累及前连合T1期声门区高分化鳞状细胞癌[J]. 山东大学耳鼻喉眼学报, 2008, 22(4): 307 -309 .
[8] 张吉仲,李大建 . 鼻内镜下鼻中隔软骨或筛骨修补鼻中隔穿孔[J]. 山东大学耳鼻喉眼学报, 2008, 22(4): 336 -337 .
[9] 于德先,张文山,皮士军,曹桂霞,李永强,马 庆,黄 健 . 中药止血愈创鼻腔填塞油纱条临床应用[J]. 山东大学耳鼻喉眼学报, 2008, 22(4): 340 -342 .
[10] 魏丽萍,刘洪英,许朝霞 . 慢性鼻窦炎内镜鼻窦手术疗效分析[J]. 山东大学耳鼻喉眼学报, 2008, 22(4): 345 -346 .
网站版权所有 © 2018 《山东大学耳鼻喉眼学报》编辑部　
地址：山东省济南市山大南路27号（250100）电话：+86-0531-88366912 E-mail: ebhxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发