基于生物信息学分析哮喘患者鼻黏膜上皮细胞DNA及α肌动蛋白2甲基化差异性表达

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摘要目的: 研究哮喘患者鼻黏膜上皮细胞中全基因组甲基化水平及α肌动蛋白2(actin alpha 2, ACTA2)基因启动子区域甲基化水平改变。方法: 利用甲基化850K芯片法检测6例哮喘患者与5例健康者鼻黏膜上皮细胞中全基因组甲基化水平，进行生物功能分析后选择ACTA2为目的基因，以重亚硫酸盐测序法检测12例哮喘患者及12例健康者ACTA2启动子区域甲基化水平。结果： 850K芯片测序结果显示，哮喘患者所有常染色体均存在不同程度的甲基化修饰，大部分发生在基因体及基因间区，10%~20%发生在启动子区，且高甲基化和低甲基化改变可存在于同一染色体上；重亚硫酸盐法测序示与健康对照组相比，哮喘组ACTA2基因启动子区出现明显高甲基化改变(P=0.001)。结论：哮喘患者鼻黏膜上皮细胞各染色体均出现广泛甲基化修饰，ACTA2基因启动子区域出现高甲基化改变。

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	张黎莎
	钱粉红

关键词 ：哮喘, 甲基化, &alpha, 肌动蛋白2

Abstract：Objective: To investigate the relationship between asthma and the differences of DNA methylation in nasal epithelium cells and to detect the methylation level of actin alpha 2(ACTA2) in asthma patients. Methods: Nasal epithelium cell samples from 6 asthma patients and 5 healthy adults were collected for the detection of methylation levels of whole genome by Illumina Infinium MethylationEPIC BeadChip. ACTA2 gene was screened out after the analysis of Gene Ontology function. Then, samples which were collected from 12 asthma patients and 12 healthy adults were detected by bisulfite genomic sequencing PCR to analyse the methylation level of ACTA2 promoter. Results: Illumina BeadChip illustrated that methylation changes were detected in all euchromosomes, most of which occured in gene body or intergenic region, only 10%-20% found in promoter. Meanwhile, hypermethylation and hypomethylation changes were found in the same chromosome; methylation level of ACTA2 promoter was higher in asthma patients than healthy adults(P=0.001). Conclusion: Asthma patients showed genomewide methylation level in nasal epithelium cells; and higher methylation level of ACTA2 promoter.

收稿日期: 2020-02-06

基金资助:国家自然科学基金资助项目(81370119)

通讯作者: 钱粉红(通讯作者)，主任医师，副教授，硕士生导师，E-mail：zhaoqian604@126.com

作者简介: 张黎莎(1994—)，女，硕士研究生

引用本文:

张黎莎，钱粉红. 基于生物信息学分析哮喘患者鼻黏膜上皮细胞DNA及α肌动蛋白2甲基化差异性表达[J]. 江苏大学学报:医学版, 2020, 30(04): 342-346. ZHANG Li-sha, QIAN Fen-hong.

Bioinformatics analysis of differential methylation of DNA and actin alpha 2 in nasal epithelium cells of asthma patients

. Journal of Jiangsu University(Medicine Edition), 2020, 30(04): 342-346.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2020/V30/I04/342

［1］Yang IV, Lozupone CA, Schwartz DA. The environment, epigenome, and asthma\[J\]. J Allergy Clin Immunol, 2017, 140(1):14-23.

［2］Tanday S. Epigenetic study identifies genes linked to asthma and allergy\[J\]. Lancet Respir Med, 2015, 3(4):274.

［3］Xu CJ, Sderhll C, Bustamante M, et al. DNA methylation in childhood asthma: an epigenomewide metaanalysis\[J\]. Lancet Respir Med, 2018, 6(5):379-388.

［4］Gao L, Liu XC, Millstein J, et al. Selfreported prenatal tobacco smoke exposure,AXL genebody methylation, and childhood asthma phenotypes\[J\]. Clin Epigenetics, 2018，10(1):98.

［5］Kyung HJ, Stephanie LD, Beizhan Y, et al. Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization\[J\]. Clin Epigenetics, 2017, 9:61.

［6］Lee HW, Park YM, Lee SJ, et al. Alphasmooth muscle actin (ACTA2) is required for metastatic potential of human lung adenocarcinoma\[J\]. Clin Cancer Res, 2013, 19(21):5879-5889.

［7］Chen J, Peters A, Papke CL, et al. Loss of smooth muscle alphaactin leads to NFκBdependent increased sensitivity to angiotensin Ⅱ in smooth muscle cells and aortic enlargement\[J\]. Circ Res, 2017,120(12):1903-1915.

［8］Merlini M, Wanner D, Nitsch RM. Tau pathologydependent remodelling of cerebral arteries precedes Alzheimer′s diseaserelated microvascular cerebral amyloid angiopathy\[J\]. Acta Neuropathol, 2016,131(5):737-752.

［9］Guo DC, Pannu H, TranFadulu V, et al. Mutations in smooth muscle alphaactin (ACTA2) lead to thoracic aortic aneurysms and dissections\[J\]. Nat Genet, 2007, 39(12):1488-1493.

［10］中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南(支气管哮喘的定义、诊断、治疗和管理方案)\[J\] . 中华结核和呼吸杂志，2008，31(3)：177-185.

［11］Neri F, Rapelli S, Krepelova A, et al. Intragenic DNA methylation prevents spurious transcription initiation\[J\]. Nature, 2017, 543(7643):72-77.

［12］梁云生，赵明，梁功平，等. 利用补丁甲基化技术构建特殊报告载体检测DNA甲基化对FCER1G基因启动子的调控活性\[J\]. 中南大学学报(医学版)，2013，38(2): 120-124.

［13］Erick F, Ting W, Cancan Q, et al. DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genomewide study\[J\]. Lancet Respir Med, 2019, 7(4):336-346.

［14］Brugha R, Lowe R, Henderson AJ, et al. DNA methylation profiles between airway epithelium and proxy tissues in children\[J\]. Acta Paediatr, 2017, 106(12): 2011-2016.

［15］Zhang X, Jocelyn MB, Burleson JD,et al. Nasal DNA methylation is associated with childhood asthma\[J\]. Epigenomics, 2018, 10(5):629-641.