变应性鼻炎甲基化基因筛选及甲基化谱的建立

Detection ofmethylated genes related to allergic rhinitis and establishment of methylation profile

目的:通过甲基化芯片筛选出变应性鼻炎(AR)相关基因异常甲基化位点,探究DNA甲基化与AR的关系。方法:提取19例AR患者和11例正常下鼻甲黏膜组织DNA制成illumina甲基化芯片,通过筛选差异性甲基化位点、Gene Ontology功能富集、KEGG通路富集和文献检索对所筛选的基因进行综合分析。结果:AR患者中出现的异常甲基化位点总共为94个,其中包括高甲基化位点51个(如ST7、LCE2D、ATRIP基因),低甲基化位点43个(如PIK3CG、TLR6、IL-4基因)。通过Gene Ontology功能富集、KEGG通路富集分析提示DNA甲基化与AR有相关趋势,ST7、LCE2D、PIK3CG基因DNA甲基化可能与AR相关,GO分析与KEGG分析差异无统计学意义。另外结合文献,TLR6基因和IL-4基因DNA甲基化可能与AR发病相关。结论:通过高通量甲基化芯片,在AR下鼻甲组织标本中筛选出不同程度的甲基化基因,提示基因甲基化是AR发病的重要原因,其之间的关联情况仍需进一步研究。

Objective:The aim of this study is to detect differentially methylated genes to allergic rhinitis(AR)based on methylation chip,and to analyze the relationship between DNA methylation and AR.Method:Illumina methylation chip were made by normal inferior turbinate mucous tissue obtained from patients(n=19)and healthy individuals(n=11).Detection of differential the sites of methylated genes,Gene Ontology enrichment,KEGG pathway enrichment database and literature search were used to analysis.Result:There were 94 aberrant methylation sites in patients with AR,including 51 hypermethylation sites(e.g.ST7,LCE2 D,ATRIP genes)and 43 hypomethylation sites(e.g.PIK3 CG,TLR6,IL-4 genes).The results of Gene Ontology enrichment and KEGG pathway enrichment indicates the DNA methylation has relative trend with AR,and DNA methylation of ST7,LCE2 D,PIK3 CG genes may be associated with AR,but the results of GO analysis and KEGG analysis were statistically significant.Moreover,literature search prompts that DNA methylation of TLR6 gene and IL-4 gene may be associated with AR.Conclusion:Varying degrees of methylated genes from inferior turbinate mucous tissue based on high-flux methylation chip hint gene methylation is an important cause of AR.The relationship between them needs further verification.