中国儿童2型炎症型哮喘单核苷酸多态性和相关基因关系的研究进展

doi:10.19983/j.issn.2096-8493.2024086

摘要/Abstract

摘要：

支气管哮喘是严重影响儿童身心健康的一种慢性炎症性疾病,根据炎症机制与表现的不同,分为2型炎症型哮喘及非2型炎症型哮喘。2型炎症型哮喘患儿数量多、占比大、症状重、疗效差。哮喘的发病机制复杂,其中遗传变异在哮喘的发生和发展中发挥着至关重要的作用,通过基因学研究设置诊断模型及个体化治疗方案具有重要意义。作者系统地回顾目前2型炎症型哮喘相关基因区域及单核苷酸多态性的研究,以更好地了解遗传因素与哮喘发生和发展之间的关系,为未来的哮喘预测诊断模型及个体化治疗方案制定提供依据。

关键词: 哮喘, 多态性, 单核苷酸, 儿童, 基因

Abstract:

Bronchial asthma is a chronic inflammatory disease that significantly impacts the physical and mental health of children. It is classified into type 2 inflammatory asthma and non-type 2 inflammatory asthma based on distinct mechanisms and manifestations of inflammation. Type 2 inflammatory asthma represents a substantial proportion of pediatric asthma cases, characterized by severe symptoms and poor clinical outcomes. The pathogenesis of asthma is complex, with genetic variation playing a critical role in its onset and progression. Developing diagnostic models and individualized treatment plans from a genetic perspective is therefore of paramount importance. The authors systematically summarizes current research on gene regions and single nucleotide polymorphisms associated with type 2 asthma, aiming to elucidate the relationship between genetic factors and the development of asthma, and to provide a foundation for future predictive diagnostic models and individualized treatment strategies for asthma.

Key words: Asthma, Polymorphism, single nucleotide polymorphism, Child, Genes

中图分类号:

R256.12

苏醒岳, 王蓓蕾, 马香. 中国儿童2型炎症型哮喘单核苷酸多态性和相关基因关系的研究进展[J]. 结核与肺部疾病杂志, 2024, 5(4): 370-375. doi: 10.19983/j.issn.2096-8493.2024086

Su XingYue, Wang Beilei, Ma Xiang. Single nucleotide polymorphisms and related genes in Chinese children with type 2 inflammatory asthma[J]. Journal of Tuberculosis and Lung Disease, 2024, 5(4): 370-375. doi: 10.19983/j.issn.2096-8493.2024086

参考文献 67

[1]	Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention (updated 2023)[EB/OL]. [2024-05-10] 2023. https://ginasthma.org/wp-content/uploads/2023/07/GINA-2023-Full-report-23_07_06-WMS.pdf.
[2]	Hong H, Fan Y, Yang Q, et al. Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation. Allergy, 2020, 75(11):2794-2804. doi:10.1111/all.14526.
[3]	谭家余, 黄湘, 李冬秀, 等. IL-10和IL-33基因单核苷酸多态性与中山市汉族儿童哮喘易感性的关系, 广东医学, 2013, 34(8):1239-1242. doi:10.3969/j.issn.1001-9448.2013.08.040.
[4]	林玛丽. IL-33基因多态性及其血清水平与广西黑衣壮儿童哮喘的相关性研究. 百色:右江民族医学院, 2018.
[5]	覃华姣. IL-33、IL1RL1基因GWAS阳性位点与广西壮族哮喘的关联研究. 南宁:广西医科大学, 2020.
[6]	李沛隆. IL-33基因多态性在广西黑衣壮族儿童哮喘易感性研究和总血清IL-33水平的相关性. 百色:右江民族医学院, 2021.
[7]	伏晓, 朱瑾, 陈漫漫, 等. IL-33在呼吸道过敏性疾病中的作用研究进展. 浙江医学, 2019, 41(5):492-495. doi:10.12056/j.issn.1006-2785.2019.41.5.2018-1097.
[8]	Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine, 2015, 75(1):14-24. doi:10.1016/j.cyto.2015.05.010. pmid: 26044597
[9]	Le Floc’h A, Allinne J, Nagashima K, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Ra antibody, is required to broadly inhibit type 2 inflammation. Allergy, 2020, 75(5):1188-1204. doi:10.1111/all.14151.
[10]	马卓然, 林娜. 广西黑衣壮族ADRB2基因、IL-4R基因多态性与儿童哮喘发病的关联研究. 右江医学, 2023, 51(6): 512-518. doi:10.3969/j.issn.1003-1383.2023.06.006.
[11]	张炫炜, 郦凡, 姚建军. IL-13、IL-4及FCERIB基因多态性对吸入糖皮质激素治疗儿童哮喘疗效的影响. 临床检验杂志, 2022, 40(12):906-911. doi:10.13602/j.cnki.jcls.2022.12.06.
[12]	龙易勤, 严提珍. 儿童哮喘与炎症基因SNP及炎症生物标志物的相关性研究. 现代预防医学, 2018, 45(20): 3712-3718.
[13]	史喜玉, 孙金霞, 马桂芳, 等. 哮喘患者IL-4基因单核苷酸多态性的病例对照研究. 科技资讯, 2019, 17(30): 218-220. doi:10.16661/j.cnki.1672-3791.2019.30.218.
[14]	Wang RS, Jin HX, Shang SQ, et al. Associations of IL-2 and IL-4 Expression and Polymorphisms With the Risks of Mycoplasma pneumoniae Infection and Asthma in Children. Arch Bronconeumol, 2015, 51(11):571-578. doi:10.1016/j.arbres.2014.11.004.
[15]	Hijazi Z, Haider MZ. Interleukin-4 gene promoter polymorphism [C590T] and asthma in Kuwaiti Arabs. Int Arch Allergy Immunol, 2000, 122(3):190-194. doi:10.1159/000024396.
[16]	任侠, 王莎莎, 王珊, 等. IL-4-590C/T基因多态性与儿童支气管哮喘关系的Meta分析. 重庆医学, 2017, 46(5):638-641,647. doi:10.3969/j.issn.1671-8348.2017.05.020.
[17]	Jin X, Zheng J. IL-4-C-590T locus polymorphism and susceptibility to asthma in children: a meta-analysis. J Pediatr (Rio J), 2021, 97(3):264-272. doi:10.1016/j.jped.2020.05.005.
[18]	Li H, Xiaoyan D, Quanhua L, et al. Single-nucleotide polymorphisms in genes predisposing to asthma in children of Chinese Han nationality. J Investig Allergol Clin Immunol, 2009, 19(5): 391-395.
[19]	Cui T, Wu J, Pan S, et al. Polymorphisms in the IL-4 and IL-4R [alpha] genes and allergic asthma. Clin Chem Lab Med, 2003, 41(7):888-892. doi:10.1515/CCLM.2003.134. pmid: 12940513
[20]	Zhang JH, Zhang M, Wang YN, et al. Correlation between IL-4 and IL-13 gene polymorphisms and asthma in Uygur children in Xinjiang. Exp Ther Med, 2019, 17(2):1374-1382. doi:10.3892/etm.2018.7096.
[21]	苏保宁. IL-4启动子-589C/T及IL-4R(rs1801275)多态性与儿童哮喘相关性的Meta分析. 中国妇幼保健, 2020, 35(17) 3320-3324. doi:10.19829/j.zgfybj.issn.1001-4411.2020.17.061.
[22]	Chiang CH, Lin MW, Chung MY, et al. The association between the IL-4, ADRβ2 and ADAM 33 gene polymorphisms and asthma in the Taiwanese population. J Chin Med Assoc, 2012, 75(12):635-643. doi:10.1016/j.jcma.2012.08.012. pmid: 23245479
[23]	廖兴娟, 朱晓萍, 李敬风, 等. 贵阳地区哮喘儿童IL-4-590C/T、IL-13-1112C/T、IL-4RαQ576R基因多态性分析. 中国免疫学杂志, 2014, 30(4):523-527. doi:10.3969/j.issn.1000-484X.2014.04.022.
[24]	桂芹, 钱桂生, 赵志强, 等. IL-4受体基因多态性与中国重庆汉族哮喘相关性研究. 重庆医学, 2006, 35(22):2055-2057. doi:10.3969/j.issn.1671-8348.2006.22.022.
[25]	孙珺, 于晓华, 陈英, 等. IL-4R基因E375A、C406R、Q576R多态性与哈尔滨地区儿童哮喘发生的相关性. 临床儿科杂志, 2010, 28(2):138-141. doi:10.3969/j.issn.1000-3606.2010.02.010.
[26]	中华医学会变态反应分会儿童过敏和哮喘学组. 四位点儿童哮喘基因预测模型与哮喘预测指数和特应性的相关性研究. 中国实用儿科杂志, 2021, 36(6): 441-446. doi:10.19538/j.ek2021060610.
[27]	Bai S, Hua L, Wang X, et al. Association of a 4-Locus Gene Model Including IL13, IL4, FCER1B, and ADRB 2 With the Asthma Predictive Index and Atopy in Chinese Han Children. J Investig Allergol Clin Immunol, 2018, 28(6):407-134. doi:10.18176/jiaci.0272.
[28]	Tian M, Liang H, Qin QZ, et al. ADRB2 polymorphisms in allergic asthma in Han Chinese children. Int Forum Allergy Rhinol, 2016, 6(4): 367-372. doi:10.1002/alr.21673.
[29]	曲相珍, 王艳军, 杨香红. 儿童哮喘IL-13、IL-4、ADRB2及FcER1B基因多态性分析. 当代临床医刊, 2023, 36(3):1-3. doi:10.3969/j.issn.2095-9559.2023.03.01.
[30]	杨善浦, 沈仁, 张林桃, 等. IL-13、IL-4、MS4A2、ADRB2基因多态性与年幼儿反复喘息发作疗效及临床转归的相关性. 临床医学研究与实践, 2021, 6(22): 28-32. doi:10.19347/j.cnki.2096-1413.202122007.
[31]	蔡旭龙. 广西黑衣壮儿童哮喘IL-4、IL-13、IL-4R和IL1R1基因多态性研究. 百色:右江民族医学院, 2018.
[32]	周广花, 张季红, 徐佩茹. 新疆维吾尔族哮喘儿童IL-13基因Arg130Gln多态性及其与血清IL-13水平的关系. 新疆医科大学学报, 2016, 39(5):622-626.
[33]	Liu L, Yue D, Hu L, et al. Relationship between interleukin-13 rs 20541 single nucleotide polymorphisms and therapeutic efficacy in children with asthma. J Int Med Resm, 2020, 48(6):300060520929179. doi:10.1177/0300060520929179.
[34]	Robinson D, Humbert M, Buhl R, et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy, 2017, 47(2): 161-175. doi:10.1111/cea.12880. pmid: 28036144
[35]	Hong SJ, Lee SY, Kim HB, et al. IL-5 and thromboxane A 2 receptor gene polymorphisms are associated with decreased pulmonary function in Korean children with atopic asthma. J Allergy Clin Immunol, 2005, 115(4): 758-763. doi:10.1016/j.jaci.2004.10.047.
[36]	张茉沁, 王璐, 许航, 等. 支气管哮喘患者白细胞介素-4、-5、-10启动子单核苷酸多态性. 中华内科杂志, 2014, 53(10): 811-813. doi:10.3760/cma.j.issn.0578-1426.2014.10.012.
[37]	Zakeri A, Russo M. Dual Role of Toll-like Receptors in Human and Experimental Asthma Models. Front Immunol, 2018, 9: 1027. doi:10.3389/fimmu.2018.01027. pmid: 29867994
[38]	杨瑞虹. TLR4基因多态性与新疆维、汉民族支气管哮喘的关联研究. 乌鲁木齐:新疆医科大学, 2011.
[39]	鲁静洁, 钱粉红, 殷小伟, 等. TLR4基因单核苷酸多态性与哮喘严重度及哮喘相关临床指标的关系. 南京医科大学学报(自然科学版), 2013, 33(9): 1231-1236. doi:10.7655/NYDXBNS20130911.
[40]	杨雪娇, 白宝鑫, 柯盈月. 哮喘患儿Toll样受体4基因多态性及其与哮喘发病的关系. 山东医药, 2023, 63(6):61-63. doi:10.3969/j.issn.1002-266X.2023.06.015.
[41]	程培培, 任磊, 周启立, 等. 维生素D水平和TLR3基因多态性与儿童肺炎支原体感染相关哮喘的关联性. 中华医院感染学杂志, 2022, 32 (2):275-279. doi:10.11816/cn.ni.2022-210420.
[42]	储卫红. TLR6 Ser249Pro基因多态性与5岁以下儿童喘息的相关性研究. 郑州:郑州大学, 2012.
[43]	邢飞, 周瑾, 姜玉新, 等. TLR7基因单核苷酸多态性与江苏淮安哮喘患者易感性的相关性研究. 中国免疫学杂志, 2022, 38(1):71-75. doi:10.3969/j.issn.1000-484X.2022.01.013.
[44]	许文苑, 丁召磊, 许振, 等. Toll样受体1基因多态性与华北地区汉族人群支气管哮喘关系的研究. 中国医药导报, 2016, 13(5):17-20.
[45]	Shiina T, Hosomichi K, Inoko H, et al. The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet, 2009, 54(1):15-39. doi:10.1038/jhg.2008.5. pmid: 19158813
[46]	侯沛君. 哮喘易感基因HLA-DQ、ORMDL3单核苷酸多态性在婴幼儿喘息中的研究.济南:山东中医药大学, 2017.
[47]	郑晓宇, 魏兵, 廖世峨, 等. HLA-DQBI基因多态性与儿童哮喘易感性及糖皮质激素疗效关系研究. 锦州医科大学学报, 2022, 43(6):71-77. doi:10.13847/j.cnki.lnmu.2022.06.013.
[48]	Kraft S, Kinet JP. New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol, 2007, 7(5): 365-378. doi:10.1038/nri2072. pmid: 17438574
[49]	Youssef LA, Schuyler M, Wilson BS, et al. Roles for the High Affinity IgE Receptor, FcεRI, of Human Basophils in the Pathogenesis and Therapy of Allergic Asthma: Disease Promotion, Protection or Both?. Open Allergy J, 2010, 3: 91-101. doi:10.2174/1874838401003010091. pmid: 25018787
[50]	Chan MA, Gigliotti NM, Aubin BG, et al. FCER2 (CD23) asthma-related single nucleotide polymorphisms yields increased IgE binding and Egr-1 expression in human B cells. Am J Respir Cell Mol Biol, 2014, 50(2): 263-269. doi:10.1165/rcmb.2013-0112OC.
[51]	高倩. IL4、IL13、ADRB2、FCER1B基因多态性与儿童过敏性哮喘易感性研究. 济南:山东中医药大学, 2022.
[52]	Kim YK, Park HW, Yang JS, et al. Association and functional relevance of E237G, a polymorphism of the high-affinity immunoglobulin E-receptor beta chain gene, to airway hyper-responsiveness. Clin Exp Allergy, 2007, 37(4):592-598. doi:10.1111/j.1365-2222.2007.02680.x. pmid: 17430357
[53]	郭素华, 林英, 李丽云, 等. 喘息患儿FcεRI-β基因多态性与临床表现、疗效及预后研究. 中国妇幼保健, 2016, 31(7):1427-1429. doi:10.7620/zgfybj.j.issn.1001-4411.2016.07.31.
[54]	马卓然. 广西黑衣壮族ADRB2、FCER1B、IL-4R位点的基因多态性与儿童哮喘的关联研究. 百色:右江民族医学院, 2023.
[55]	陆玉娇, 杨月容, 陈宇, 等. ADRB2和FCER1B基因多态性与壮族咳嗽变异性哮喘患儿治疗效果及肺功能改善情况的相关性. 广西医学, 2022, 44(22):2618-2623. doi:10.11675/j.issn.0253-4304.2022.22.08.
[56]	邱玉明, 李剑雄, 肖少娴. FCER2基因rs28364072位点多态性与哮喘的相关性. 实用医学杂志, 2017, 33(3):346-349. doi:10.3969/j.issn.1006-5725.2017.03.004.
[57]	叶冬梅, 李明, 张泉. ADRB2、GLCCI1、FCER2基因多态性与小儿哮喘治疗效果以及患儿肺功能的关系. 当代医学, 2019, 25(24):11-15. doi:10.3969/j.issn.1009-4393.2019.24.004.
[58]	廉悦. ADRB2、FCER2、GLCCI1、CRHR1基因多态性与哮喘药物治疗的相关性研究. 大理:大理大学, 2019.
[59]	任丹阳, 李云巍, 涂彩霞, 等. ADRB2、GLCCI1、FCER2基因检测在2例难治性哮喘患儿个体化用药中的实践. 中国药房, 2018, 29(5):659-662. doi:10.6039/j.issn.1001-0408.2018.05.21.
[60]	李剑雄, 邱玉明, 李慧. 哮喘患者FCER2基因T2206C位点多态性与吸入糖皮质激素治疗反应的相关性. 广东医学, 2017, 38(19):2969-2971. doi:10.13820/j.cnki.gdyx.2017.19.008.
[61]	Cazzola M, Page CP, Matera MG, et al. Revisiting asthma pharmacotherapy: where do we stand and where do we want to go?. Eur Respir J, 2023, 62(2):2300700. doi:10.1183/13993003.00700-2023.
[62]	Liang SQ, Chen XL, Deng JM, et al. Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies. PLoS One, 2014, 9(8):e104488. doi:10.1371/journal.pone.0104488.
[63]	蔡明轩, 魏兵, 廖世峨, 等. ADRB2基因调控区多态性与儿童哮喘易感性的相关性研究. 中国当代儿科杂志, 2021, 23(11):1132-1140. doi:10.7499/j.issn.1008-8830.2108054.
[64]	陈慧芬, 张德平, 邱玉英, 等. ADRB2基因多态性/单倍型与中国汉族人群哮喘的相关性. 南京医科大学学报(自然科学版), 2014, 34(3):323-329. doi:10.7655/NYDXBNS20140309.
[65]	张世楠, 魏兵, 蔡明轩, 等. ADRB2基因调控区多态性对SABA治疗儿童哮喘急性发作疗效的影响. 中国药房, 2023, 34(6): 714-718,723. doi:10.6039/j.issn.1001-0408.2023.06.14.
[66]	任丹阳, 涂彩霞, 李惠英, 等. ADRB2(rs1042713)基因多态性对抗胆碱能药物治疗难治性哮喘患儿疗效的影响. 中国药房, 2019, 30(23): 3265-3270. doi:10.6039/j.issn.1001-0408.2019.23.17.
[67]	Greene CS, Tan J, Ung M, et al. Big data bioinformatics. J Cell Physiol, 2014, 229(12):1896-1900. doi:10.1002/jcp.24662. pmid: 24799088