摘要
目的 利用多种广义生物信息学技术从遗传流行病学方向发掘变应性鼻炎易感基因,发扬中医药在变应性鼻炎疾病管理中的优势,助力于变应性鼻炎预防。方法 利用孟德尔随机化及汇总数据的孟德尔随机化分别获取蛋白质及基因表达水平遗传变异相关基因,取交集获取对遗传变异影响较大的变应性鼻炎易感基因,并利用基因集数据对其进行表达富集分析,探寻基因生物功能。利用共定位分析进一步筛选出关键变应性鼻炎易感基因,并对其进行可药性分析。同时利用分子对接及中药数据库筛选关键变应性鼻炎易感基因相关活性成分及潜在干预中药。结果 筛选出6个变应性鼻炎易感基因TLR1、NFKB1、TNFSF8、TAPBP、ITPKA、MAP1LC3A,其表达与Toll样受体、NOD样受体、吞噬细胞等免疫与炎症相关成分功能密切相关,同时参与激素的分解代谢。其中TLR1、ITPKA是关键变应性鼻炎易感基因且具有开发靶向药物潜力。活性成分中丙酸成分具有防治变应性鼻炎的潜力。通过靶点预测补益肺脾药是靶向关键变应性鼻炎易感基因主要潜在中药。而“肺脾同治,气阴同调”或是预防变应性鼻炎的中药配伍关键思路之一。结论 挖掘变应性鼻炎易感基因和潜在干预中药,为变应性鼻炎的研究提供了新的视角,实现遗传流行病学在变应性鼻炎领域的中医药临床转化。
Objective A variety of generalized bioinformatics techniques were used to explore the susceptible genes of allergic rhinitis(AR)from the direction of genetic epidemiology to promote the advantages of traditional Chinese medicine in the management of allergic rhinitis and contribute to the prevention of AR.Methods We first conducted Mendelian randomization(MR)and eQTL-based summary-data-based MR(SMR)to obtain genes related to genetic variation at protein expression level and gene expression level respectively,and the intersection was used to obtain the AR susceptible genes that had a greater impact on genetic variation,and the expression enrichment analysis was conducted using gene set data to explore the biological functions of genes.The key susceptible genes of AR were further selected by performed colocalization analysis and their drugabilities were analyzed.At the same time,molecular docking and Chinese medicine database were used to screen key AR susceptible gene-related active ingredients and potential intervention Chinese medicines.Results TLR1,NFKB1,TNFSF8,TAPBP,ITPKA and MAP1LC3A were identified as susceptible genes for AR.These gene expression was closely related to the function of Toll-like receptors,NOD-like receptors,phagocytes and other immune and inflammatory components,and they were also involved in the catabolism of hormones.TLR1 and ITPKA were the key susceptible genes and had the potential to develop targeted drugs.The propionic acid component of the active ingredient had the potential to prevent and treat allergic rhinitis.The main potential traditional Chinese medicines targeting the key susceptible genes were tonifying lung and spleen medicines.And“lung and spleen are treated together,qi and yin are in harmony”emerges as a pivotal strategy of compatibility in the prevention of AR.Conclusion Exploring the susceptible genes of AR and the potential intervention of Chinese medicine provides a new perspective for the study of AR,and realizes the clinical transformation of genetic epidemiology
作者
田心语
唐心浩
李梓墨
陈小宁
袁海洲
沙志荣
史军
TIAN Xinyu;TANG Xinhao;LI Zimo;CHEN Xiaoning;YUAN Haizhou;SHA Zhirong;SHI Jun(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;First Clinical College,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Research Association for the Development of Undertakings for the Aged,Nanjing 210008,China;Department of Medicine,Jianghan University,Wuhan 430056,China;Huishan District Hospital of Traditional Chinese Medicine,Wuxi 214000,China;Qidong Hospital of Traditional Chinese Medicine,Nantong 226200,China)
出处
《中草药》
CAS
CSCD
北大核心
2024年第22期7773-7785,共13页
Chinese Traditional and Herbal Drugs
基金
江苏省卫生健康委员会重点项目(ZD2021016)
江苏省中医药管理局“省名老中医陈小宁专家传承工作室”建设项目(苏中医科教[2021]7号)
国家级大学生创新训练计划项目(202210315128Z)
南京中医药大学2022年“罗林秀杯”大学生创新训练项目
南京中医药大学2023年中医药人工智能“揭榜挂帅”项目。
关键词
变应性鼻炎
全基因组关联研究
孟德尔随机化
虚拟药物筛选
肺脾同治
丙酸
槲皮素
红藻氨酸
allergic rhinitis
genome-wide association study
Mendelian randomization
virtual drug screening
treating lung and spleen together
augustic acid
quercetin
kainic acid
