本文選題：銀屑病　切入點(diǎn)：DNA甲基化　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景:銀屑病(Psoriasis,Ps)是一種常見的慢性炎癥性復(fù)發(fā)性皮膚病,其確切病因尚不完全清楚。銀屑病依據(jù)臨床特征、患者發(fā)病年齡、皮損面積和皮損嚴(yán)重程度(Psoriasis Area and Severity Index,PASI)等劃分成多種亞型。DNA甲基化(DNA methylation,DNAm)與人類發(fā)育和各類疾病發(fā)生的關(guān)系密切,多項(xiàng)表觀遺傳學(xué)研究表明DNA甲基化與銀屑病存在關(guān)聯(lián)性,并且對(duì)銀屑病易感基因的表達(dá)水平具有調(diào)控作用,進(jìn)而影響人群患銀屑病的風(fēng)險(xiǎn)性。研究目的:本研究利用課題組前期開展的中國(guó)漢族人群銀屑病全基因組表觀遺傳學(xué)DNA甲基化數(shù)據(jù)進(jìn)行疾病分子亞型分型,并進(jìn)一步比較不同亞型銀屑病臨床特征和3個(gè)易感基因(DEFB4、IL22和LCE3C)拷貝數(shù)變異(Copy number variant,CNV)之間的差異性,從分子學(xué)和遺傳學(xué)角度指導(dǎo)銀屑病的治療和管理。實(shí)驗(yàn)數(shù)據(jù)和方法:使用一致聚類法(Consensus Clustering)對(duì)銀屑病DNA甲基化數(shù)據(jù)進(jìn)行集群分析,將銀屑病劃分為不同的分子亞型(k),運(yùn)用輪廓寬度分析(Silhouette)等方法檢測(cè)集群結(jié)果顯著性從而判定劃分亞型(k)。利用方差分析等統(tǒng)計(jì)學(xué)方法對(duì)銀屑病不同分子亞型間的臨床特征和3個(gè)基因的CNV進(jìn)行比較分析。結(jié)果:通過一致聚類法分析將銀屑病分為三型,其中I型包含29例,II型包含39例,III型包含46例。三種不同亞型的臨床特征(性別、發(fā)病年齡、吸煙情況、PASI評(píng)分)以及3個(gè)易感基因(DEFB4、IL22和LCE3C)的CNV進(jìn)行比較分析發(fā)現(xiàn):三組在性別構(gòu)成比例、PASI評(píng)分等方面的差異性不具有統(tǒng)計(jì)學(xué)意義;I型中大于40歲(晚發(fā)型)的患者比例明顯高于II型和III型,三組之間的差異具有統(tǒng)計(jì)學(xué)意義;III型中曾經(jīng)吸煙者比例最小,從不吸煙者比例最大,三組之間具有邊緣性統(tǒng)計(jì)學(xué)差異;三組銀屑病亞型之間DEFB4和LCE3C的CNV差異不存在統(tǒng)計(jì)學(xué)意義,而IL22的CNV差異性顯著。結(jié)論:本研究首次利用DNA甲基化數(shù)據(jù)將銀屑病劃分為三種亞型,比較分析發(fā)現(xiàn)三種亞型之間的發(fā)病年齡、患者吸煙情況以及基因IL22的CNV存在統(tǒng)計(jì)學(xué)差異。利用DNA甲基化數(shù)據(jù)對(duì)銀屑病進(jìn)行分子亞型分析,有利于從分子學(xué)和遺傳學(xué)角度指導(dǎo)銀屑病的治療和管理。
[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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R758.63

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本文編號(hào)：1588859