本文選題：銀屑病 + LCE　； 參考：《安徽醫(yī)科大學(xué)》2012年碩士論文

【摘要】：研究背景：銀屑病(Psoriasis)是一種常見的以慢性炎癥反應(yīng)和表皮異常增生為主要特征的免疫介導(dǎo)的皮膚病。目前普遍認(rèn)為大量炎癥細(xì)胞如樹突狀細(xì)胞、巨噬細(xì)胞、中性粒細(xì)胞及角質(zhì)細(xì)胞和某些細(xì)胞因子在銀屑病發(fā)病機(jī)制中發(fā)揮著重要作用。我們前期全基因組關(guān)聯(lián)分析（Genome-wide association study, GWAS）研究已經(jīng)證實LCE基因為銀屑病的易感基因，并同時發(fā)現(xiàn)CLEC16A基因與銀屑病的發(fā)病存在關(guān)聯(lián)性(SNP rs193756,OR=0.8, P=0.0004)。有研究證實LCE基因簇編碼表皮屏障蛋白，后者的表達(dá)受到促炎因子的調(diào)節(jié)，而CLEC16A基因與自身免疫性疾病多發(fā)性硬化相關(guān)，其編碼的蛋白在一些炎癥細(xì)胞中呈高水平表達(dá)。最近已有研究報道證實LCE與HLA-C、MHC及IL12B等區(qū)域或基因間存在交互作用并共同影響了銀屑病的發(fā)病，故有理由推測CLEC16A基因與LCE基因也可能存在交互作用并共同參與了銀屑病的發(fā)生過程。 目的：驗證LCE rs4112788和CLEC16A rs193756各基因型與銀屑病的相關(guān)性，分析LCE基因和CLEC16A基因的交互作用對銀屑病發(fā)病的影響。 方法：本研究首先對LCE rs4112788和CLEC16A rs193756的前期GWAS研究相關(guān)數(shù)據(jù)進(jìn)行整理，兩者的基因分型數(shù)據(jù)均來自于我們團(tuán)隊前期GWAS研究，即5101份銀屑病病例和6183份正常對照，，均為中國漢族人。通過建立LCE rs4112788和CLEC16A rs193756的四種基因交互作用模型，用卡方檢驗分析LCE rs4112788和CLEC16A rs193756各基因型與銀屑病的相關(guān)性，用logistic回歸方法分析LCE和CLEC16A的四種基因交互作用模型與銀屑病的關(guān)系。 結(jié)果： LCE rs411278-CC為銀屑病發(fā)病的風(fēng)險基因型(OR=1.76, P=5.90×10-5)，CLEC16A rs193576各基因型與銀屑病無明顯相關(guān)。進(jìn)一步構(gòu)建LCE rs4112788和CLEC16A rs193756的四種交互作用模型結(jié)果顯示，LCE rs4112788-CC或-TC和CLEC16A rs193756-GG的交互作用對銀屑病發(fā)病風(fēng)險有提示作用(OR=1.84, P=0.0605)，而LCE rs4112788-CC和CLEC16A rs193756-GG的交互作用與銀屑病發(fā)病風(fēng)險的關(guān)聯(lián)性更加顯著(OR=1.57, P=0.0053)。 結(jié)論：本研究發(fā)現(xiàn)LCE基因和CLEC16A基因在中國漢族人銀屑病發(fā)病過程中有顯著的交互作用，LCE rs4112788-CC和CLEC16A rs193756-GG可能為銀屑病發(fā)病的風(fēng)險基因型，兩者可能在表皮屏障修復(fù)和炎癥反應(yīng)的某些通路中存在交互作用進(jìn)而導(dǎo)致銀屑病的發(fā)病或加重。
[Abstract]:Background: psoriasis (Psoriasis) is a common immune-mediated dermatosis characterized by chronic inflammatory reaction and epidermal dysplasia.It is widely believed that a large number of inflammatory cells such as dendritic cells macrophages neutrophils keratinocytes and some cytokines play an important role in the pathogenesis of psoriasis.Genome-wide association study (GWASA) has confirmed that LCE gene is susceptible to psoriasis, and has also found that there is a correlation between CLEC16A gene and psoriasis, such as SNPrs193756 OR0.8and P0. 0004.Some studies have confirmed that LCE gene cluster encodes epidermal barrier protein, the latter expression is regulated by proinflammatory factor, while CLEC16A gene is associated with multiple sclerosis of autoimmune disease, and its encoded protein is highly expressed in some inflammatory cells.Recent studies have shown that there is interaction between LCE and HLA-CmHC and IL12B regions or genes, which may influence the pathogenesis of psoriasis.It is reasonable to speculate that the interaction between CLEC16A gene and LCE gene may be involved in the pathogenesis of psoriasis.Aim: to investigate the relationship between LCE rs4112788 and CLEC16A rs193756 genotypes and psoriasis, and to analyze the effect of LCE gene and CLEC16A gene interaction on psoriasis.Methods: in this study, the data of LCE rs4112788 and CLEC16A rs193756 pre-study on GWAS were collected. The genotyping data were collected from 5101 psoriasis cases and 6183 normal controls in our team. All of them were Chinese Han people.By establishing four gene interaction models of LCE rs4112788 and CLEC16A rs193756, the correlation between the genotype of LCE rs4112788 and CLEC16A rs193756 and psoriasis was analyzed by chi-square test. The relationship between the four gene interaction models of LCE and CLEC16A and psoriasis was analyzed by logistic regression method.Results: LCE rs411278-CC was the risk genotype of psoriasis. There was no significant correlation between LCE rs411278-CC and psoriasis.Four kinds of interaction models of LCE rs4112788 and CLEC16A rs193756 were further constructed. The results showed that the interaction of LCE rs4112788-CC or -TC and CLEC16A rs193756-GG had a positive effect on the risk of psoriasis. The interaction between LCE rs4112788-CC and CLEC16A rs193756-GG was associated with the risk of psoriasis.The correlation was more significant in ORA 1.57, P0. 0053.Conclusion: in this study, we found that LCE gene and CLEC16A gene have significant interaction in the pathogenesis of psoriasis in Chinese Han nationality. LCE rs4112788-CC and CLEC16A rs193756-GG may be risk genotypes of psoriasis.They may interact with each other in some pathways of epidermal barrier repair and inflammatory response, which may lead to the pathogenesis or aggravation of psoriasis.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R758.63

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 楊森,魏生才,張學(xué)軍,陳珊宇,王紅艷;尋常型銀屑病誘因流行病學(xué)研究[J];中國麻風(fēng)皮膚病雜志;2000年03期

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