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首页> 外文期刊>Allergy >Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics.
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Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics.

机译：鼻息肉的全基因组甲基化概况：与哮喘患者中阿司匹林超敏反应的关系。

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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.
机译：背景：除了阿司匹林耐受性哮喘（AIA）中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。但是，许多影响尚不清楚。目的：本研究旨在评估有或没有阿司匹林超敏反应的血液和息肉组织中全基因组的甲基化状态。方法：使用5名AIA患者和4名阿司匹林耐受性哮喘（ATA）患者，通过微阵列分析检测了鼻息肉和外周血细胞全基因组DNA甲基化水平。结果：在AIA患者的鼻息肉中，在296个基因的332个基因座中检测到甲基化过高，而在141个基因的158个基因座中检测到甲基化过低。基因本体论和途径富集分析显示，涉及淋巴细胞增殖，细胞增殖，白细胞活化，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被低甲基化，而涉及外胚层发育，止血，伤口愈合，钙的基因离子结合和氧化还原酶活性被甲基化。在花生四烯酸途径中，PGDS，ALOX5AP和LTB4R被低甲基化，而PTGES被高甲基化。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。在这项研究中确定的基因和途径可能与哮喘患者中阿司匹林超敏反应的存在有关，因此是未来研究的有吸引力的目标。

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