LCE和CLEC16A基因交互作用与中国汉族人银屑病的相关性研究

发布时间：2018-04-16 21:06

本文选题：银屑病 + LCE　；参考：《安徽医科大学》2012年硕士论文

【摘要】：研究背景：银屑病(Psoriasis)是一种常见的以慢性炎症反应和表皮异常增生为主要特征的免疫介导的皮肤病。目前普遍认为大量炎症细胞如树突状细胞、巨噬细胞、中性粒细胞及角质细胞和某些细胞因子在银屑病发病机制中发挥着重要作用。我们前期全基因组关联分析（Genome-wide association study, GWAS）研究已经证实LCE基因为银屑病的易感基因，并同时发现CLEC16A基因与银屑病的发病存在关联性(SNP rs193756,OR=0.8, P=0.0004)。有研究证实LCE基因簇编码表皮屏障蛋白，后者的表达受到促炎因子的调节，而CLEC16A基因与自身免疫性疾病多发性硬化相关，其编码的蛋白在一些炎症细胞中呈高水平表达。最近已有研究报道证实LCE与HLA-C、MHC及IL12B等区域或基因间存在交互作用并共同影响了银屑病的发病，故有理由推测CLEC16A基因与LCE基因也可能存在交互作用并共同参与了银屑病的发生过程。目的：验证LCE rs4112788和CLEC16A rs193756各基因型与银屑病的相关性，分析LCE基因和CLEC16A基因的交互作用对银屑病发病的影响。方法：本研究首先对LCE rs4112788和CLEC16A rs193756的前期GWAS研究相关数据进行整理，两者的基因分型数据均来自于我们团队前期GWAS研究，即5101份银屑病病例和6183份正常对照，，均为中国汉族人。通过建立LCE rs4112788和CLEC16A rs193756的四种基因交互作用模型，用卡方检验分析LCE rs4112788和CLEC16A rs193756各基因型与银屑病的相关性，用logistic回归方法分析LCE和CLEC16A的四种基因交互作用模型与银屑病的关系。结果： LCE rs411278-CC为银屑病发病的风险基因型(OR=1.76, P=5.90×10-5)，CLEC16A rs193576各基因型与银屑病无明显相关。进一步构建LCE rs4112788和CLEC16A rs193756的四种交互作用模型结果显示，LCE rs4112788-CC或-TC和CLEC16A rs193756-GG的交互作用对银屑病发病风险有提示作用(OR=1.84, P=0.0605)，而LCE rs4112788-CC和CLEC16A rs193756-GG的交互作用与银屑病发病风险的关联性更加显著(OR=1.57, P=0.0053)。结论：本研究发现LCE基因和CLEC16A基因在中国汉族人银屑病发病过程中有显著的交互作用，LCE rs4112788-CC和CLEC16A rs193756-GG可能为银屑病发病的风险基因型，两者可能在表皮屏障修复和炎症反应的某些通路中存在交互作用进而导致银屑病的发病或加重。
[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.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.63

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