基于DNA甲基化的中国汉族人群银屑病分子亚型分析

发布时间：2018-03-09 14:07

本文选题：银屑病　切入点：DNA甲基化　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究背景:银屑病(Psoriasis,Ps)是一种常见的慢性炎症性复发性皮肤病,其确切病因尚不完全清楚。银屑病依据临床特征、患者发病年龄、皮损面积和皮损严重程度(Psoriasis Area and Severity Index,PASI)等划分成多种亚型。DNA甲基化(DNA methylation,DNAm)与人类发育和各类疾病发生的关系密切,多项表观遗传学研究表明DNA甲基化与银屑病存在关联性,并且对银屑病易感基因的表达水平具有调控作用,进而影响人群患银屑病的风险性。研究目的:本研究利用课题组前期开展的中国汉族人群银屑病全基因组表观遗传学DNA甲基化数据进行疾病分子亚型分型,并进一步比较不同亚型银屑病临床特征和3个易感基因(DEFB4、IL22和LCE3C)拷贝数变异(Copy number variant,CNV)之间的差异性,从分子学和遗传学角度指导银屑病的治疗和管理。实验数据和方法:使用一致聚类法(Consensus Clustering)对银屑病DNA甲基化数据进行集群分析,将银屑病划分为不同的分子亚型(k),运用轮廓宽度分析(Silhouette)等方法检测集群结果显著性从而判定划分亚型(k)。利用方差分析等统计学方法对银屑病不同分子亚型间的临床特征和3个基因的CNV进行比较分析。结果:通过一致聚类法分析将银屑病分为三型,其中I型包含29例,II型包含39例,III型包含46例。三种不同亚型的临床特征(性别、发病年龄、吸烟情况、PASI评分)以及3个易感基因(DEFB4、IL22和LCE3C)的CNV进行比较分析发现:三组在性别构成比例、PASI评分等方面的差异性不具有统计学意义;I型中大于40岁(晚发型)的患者比例明显高于II型和III型,三组之间的差异具有统计学意义;III型中曾经吸烟者比例最小,从不吸烟者比例最大,三组之间具有边缘性统计学差异;三组银屑病亚型之间DEFB4和LCE3C的CNV差异不存在统计学意义,而IL22的CNV差异性显著。结论:本研究首次利用DNA甲基化数据将银屑病划分为三种亚型,比较分析发现三种亚型之间的发病年龄、患者吸烟情况以及基因IL22的CNV存在统计学差异。利用DNA甲基化数据对银屑病进行分子亚型分析,有利于从分子学和遗传学角度指导银屑病的治疗和管理。
[Abstract]:Background: psoriasis is a common chronic inflammatory recurrent dermatosis, the exact etiology of which is not completely clear. Psoriasis is based on clinical features, age of onset of psoriasis. Psoriasis Area and Severity Severity (PASI) were divided into several subtypes. DNA methylation was closely related to human development and the occurrence of various diseases. Epigenetic studies showed that DNA methylation was associated with psoriasis. The expression level of psoriatic susceptibility gene was regulated. Objective: to study the molecular subtypes of psoriasis by using the DNA methylation data of the whole genome of psoriasis in Chinese Han nationality population. The clinical characteristics of different subtypes of psoriasis and the differences of copy number variation of three susceptible genes, DEFB4nIL22 and LCE3C, were compared. To guide the treatment and management of psoriasis from the molecular and genetic perspectives. Experimental data and methods: the DNA methylation data of psoriasis were analyzed by cluster analysis using consensus clustering. The psoriasis was divided into different molecular subtypes, and the results of cluster were detected significantly by silhouette.A statistical method, such as analysis of variance, was used to determine the presence of different molecular subtypes of psoriasis. Results: psoriasis was classified into three types by consistent cluster analysis. Type I included 29 patients with type II, including 39 patients with type III and 46 patients with different subtypes of clinical features (sex, age of onset, age of onset). A comparative analysis of the smoking status and the CNV of three susceptible genes, DEFB4, IL22 and LCE3C, showed that there was no significant difference between the three groups in sex composition ratio and PASI score in patients older than 40 years old (late hairstyle). The proportion of patients was significantly higher than that of type II and III. The difference among the three groups was statistically significant. Among the three groups, the proportion of former smokers was the smallest, the proportion of non-smokers was the largest, and there was a marginal statistical difference among the three groups. There was no significant difference in CNV between DEFB4 and LCE3C among the three groups of psoriatic subtypes. Conclusion: this study used DNA methylation data to classify psoriasis into three subtypes for the first time. There were statistical differences in smoking status and CNV of gene IL22 in patients. Using DNA methylation data to analyze the molecular subtypes of psoriasis was helpful to guide the treatment and management of psoriasis from the point of view of molecular and genetics.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.63

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