系统性红斑狼疮患者外周血单个核细胞LBH基因mRNA表达研究

发布时间：2018-05-09 04:23

本文选题：LBH + 系统性红斑狼疮　；参考：《安徽医科大学》2015年硕士论文

【摘要】：研究背景系统系性红斑狼疮(Systemic lupus erythematosus,SLE)是一种可累及全身多个器官和系统的自身免疫性疾病,临床表现复杂,发病机制尚未明确。目前认为与遗传、免疫、病毒感染、药物、激素和环境等因素有关,其中遗传在SLE的发病中起着重要作用。近年来随着人类基因组计划(Human Genome Project,HGP)以及国际人类基因组单体型图计划(Human Haplotype Map,Hap Map)的完成和廉价高效的高通量基因分型技术的出现,全基因组关联分析(Genome-wide association study,GWAS)对不同的种族人群SLE患者研究发现了许多新的易感基因和位点。本课题组前期完成了中国汉族人群SLE全基因组关联研究,发现了多个SLE易感基因,并建立了1,047例和1,205例健康对照,覆盖全基因组62万个SNPs的基因分型数据库。通过对该数据库中候选SNPs的进一步验证,新发现位于2p23.1的LBH基因与SLE易感性密切相关。为了鉴定出该基因与中国人群SLE易感性真正相关联的SNPs,并且揭示其在SLE发病中的相关作用机制。本实验运用实时荧光定量聚合酶链反应技术,分析LBH基因m RNA在病例和健康对照中的表达情况,进一步探讨LBH基因在SLE发病机制中的作用。目的探讨LBH基因在系统性红斑狼疮(SLE)患者外周血单个核细胞中的表达情况,以及与SLE疾病活动指数(SLEDAI)、单核苷酸多态性(SNPs)位点rs7579944和rs906868的相关性。方法本研究采集62例SLE患者和69例正常对照的临床资料及血样,从外周血单个核细胞(PBMC)中提取m RNA并且逆转录为c DNA,利用ABI 7900型高通量荧光定量PCR技术检测外周血单个核细胞中LBH基因m RNA表达量;应用Sequenom Mass Array技术对所有病例对照SNP rs7579944和rs906868位点进行基因分型;运用SPSS20.0软件对数据进行统计分析。结果SLE患者LBH基因m RNA表达低于正常对照组,差异具有显著性(P0.001);LBH基因m RNA表达水平与SLEDAI和SNP rs7579944和rs906868基因型之间无相关性。结论LBH基因的表达异常提示该基因在SLE的发病机制发生中可能起着某种重要的调节作用。
[Abstract]:Background systemic lupus erythematosus (SLEs) is an autoimmune disease involving multiple organs and systems of the whole body. It is thought to be related to heredity, immunity, virus infection, drugs, hormones and environment, among which heredity plays an important role in the pathogenesis of SLE. In recent years, with the completion of the Human Genome Project (HGP) and the International Human Genome haplotype Project (HGP) and the emergence of cheap and efficient high-throughput genotyping techniques, Genome-wide association studyGWASA has found many new susceptibility genes and loci in SLE patients from different ethnic groups. The whole SLE genome association study of Chinese Han population was completed in the early stage of this study. Several SLE susceptibility genes were found and the genotyping database covering 620000 SNPs was established in 1047 cases and 1205 healthy controls. Through further validation of candidate SNPs in the database, it was found that the LBH gene located in 2p23.1 was closely related to SLE susceptibility. In order to identify the SNPs associated with the susceptibility of SLE in Chinese population, and to reveal the related mechanism of SNPs in the pathogenesis of SLE. In this study, real-time fluorescence quantitative polymerase chain reaction was used to analyze the expression of m RNA of LBH gene in patients and healthy controls, and to further explore the role of LBH gene in the pathogenesis of SLE. Objective to investigate the expression of LBH gene in peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE) and its association with rs7579944 and rs906868 at SLEDAI (single nucleotide polymorphism) site. Methods the clinical data and blood samples of 62 patients with SLE and 69 normal controls were collected. M RNA was extracted from peripheral blood mononuclear cells (PBMC) and reverse transcripted to c DNA. The expression of LBH gene m RNA in peripheral blood mononuclear cells (PBMC) was detected by high throughput quantitative PCR (ABI 7900). The SNP rs7579944 and rs906868 loci were genotyped by Sequenom Mass Array, and the data were statistically analyzed by SPSS20.0 software. Results the expression of LBH gene m RNA in patients with SLE was lower than that in normal controls. There was no significant correlation between the expression of m RNA and SLEDAI, SNP rs7579944 and rs906868 genotypes. Conclusion the abnormal expression of LBH gene may play an important role in the pathogenesis of SLE.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R593.241

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