Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics
Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics
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DOI：
10.1111/j.1398-9995.2010.02514.x
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发表时间：
2011-05-01
期刊：
影响因子：
12.4
通讯作者：
Park, C. -S.
中科院分区：
文献类型：
--
作者：
Cheong, H. S.;Park, S. -M.;Park, C. -S.
P>背景：阿司匹林不耐受哮喘（AIA）除了导致花生四烯酸代谢失调外，阿司匹林乙酰水杨酸（ASA）还对炎症和免疫产生影响；目的：本研究的目的是评估有或没有阿司匹林过敏症的血液和息肉组织中全基因组的甲基化状态。方法：通过微阵列分析，使用 5 名 AIA 受试者和 4 名阿司匹林耐受性哮喘（ATA）受试者，检测鼻息肉和外周血细胞中的全基因组 DNA 甲基化水平。结果：在 AIA 患者的鼻息肉中，在 332 个位点检测到高甲基化。 296 个基因，141 个基因的 158 个基因座检测到低甲基化。基因本体和通路富集分析显示，涉及淋巴细胞增殖、细胞增殖、白细胞激活、细胞因子生物合成、细胞因子分泌、免疫反应、炎症和免疫球蛋白结合的基因低甲基化，而涉及外胚层发育、止血、伤口愈合、钙离子结合和氧化还原酶活性的基因高甲基化。在花生四烯酸途径中，PGDS、ALOX5AP和LTB4R低甲基化，而PTGES高甲基化。结论：AIA患者的鼻息肉具有影响337个基因的特征性甲基化模式。本研究中确定的基因和途径可能与哮喘患者阿司匹林过敏的存在有关，因此是未来研究的有吸引力的目标。
P>Background:In addition to the dysregulation of arachidonic acid metabolism in aspirin-intolerant asthma (AIA), aspirin acetylsalicylic acid (ASA) exerts effects on inflammation and immunity; however, many of these effects are unknown.Objective:The aim of the study was to evaluate the methylation status of whole genome in blood and polyp tissues with and without aspirin hypersensitivity.Methods:Genome-wide DNA methylation levels in nasal polyps and peripheral blood cells were examined by microarray analysis using five subjects with AIA and four subjects with aspirin-tolerant asthma (ATA).Results:In the nasal polyps of the patients with AIA, hypermethylation was detected at 332 loci in 296 genes, while hypomethylation was detected at 158 loci in 141 genes. Gene ontologic and pathway enrichment analyses revealed that genes involved in lymphocyte proliferation, cell proliferation, leukocyte activation, cytokine biosynthesis, cytokine secretion, immune responses, inflammation, and immunoglobulin binding were hypomethylated, while genes involved in ectoderm development, hemostasis, wound healing, calcium ion binding, and oxidoreductase activity were hypermethylated. In the arachidonate pathway, PGDS, ALOX5AP, and LTB4R were hypomethylated, whereas PTGES was hypermethylated.Conclusion:The nasal polyps of patients with AIA have characteristic methylation patterns affecting 337 genes. The genes and pathways identified in this study may be associated with the presence of aspirin hypersensitivity in asthmatics and are therefore attractive targets for future research.