原发性痛风甲基化谱的研究

Study of DNA methylation profile in gout based on DNA chip technique

目的应用基因芯片技术对痛风患者基因甲基化谱进行研究,为进一步研究探讨痛风的发病机制提供依据。方法随机选取门诊确诊为原发性痛风的3例男性患者(痛风组)和3例男性健康体检者(对照组),采用基因芯片技术对两组受试者进行全基因组CpG岛的DNA甲基化检测,筛选差异甲基化位点,采用Gene Ontology分析和Pathway分析对筛选基因进行功能分类和通路分析。结果痛风组与对照组相比,共有20 426个CpG位点甲基化水平发生改变,涉及10 063个基因,其中有5 719个高甲基化位点,14 707个低甲基化位点。Gene Ontology分析显示,差异性甲基化基因主要参与调控小GTPase介导的信号转导、神经系统发育、神经形成、亲同抗原的细胞黏附以及神经元的分化等;Pathway分析显示,差异性甲基化基因参与了趋化因子细胞通路、FcγR介导的吞噬作用通路、B细胞受体信号通路以及T细胞受体信号通路等炎性通路。结论 DNA甲基化可能与痛风的发病和急性期炎性反应相关,但还需进一步探究。

Objective To investigate the DNA methylation profile in gout with gene chip technique.Methods Three male patients with primary gout(gout group)and 3 healthy male subjects(control group)were recruited in the study.DNA methylation was detected and aberrant methylation sites were screened with gene chip of Infinium.Meanwhile,the function of abnormal methylation genes was analyzed with Gene Ontology analysis and Pathway analysis.Results Compared with the healthy control group,the gout group had 20 426 significantly differential methylated sites involved in 10 063 genes.Among them,5 719 were high methylation sites and 14 707 were low methylation sites.Gene Ontology biological process analysis showed that the aberrant methylation genes mainly involved in the regulation of small GTPase mediated signal transduction,nervous system development,neurogenesis,homophilic cell adhesion,neuron differentiation and so on.Pathway analysis demonstrated that the aberrant methylation genes played a part in chemokine signaling pathway,Fc gamma R-mediated phagocytosis,B cell receptor signaling pathway,T cell receptor signaling pathway and so forth.Conclusion DNA methylation may play a role in the development of gout and inflammatory response at acute phase.However,further studies are needed.