STAT4基因单核苷酸多态性及其mRNA水平与系统性红斑狼疮的关联性研究

发布时间：2018-03-29 12:12

本文选题：基因　切入点：系统性红斑狼疮　出处：《安徽医科大学》2017年硕士论文

【摘要】：研究一STAT4基因多态性与系统性红斑狼疮临床表型的相关性研究目的本研究主要是研究STAT4基因位点rs7574865与系统性红斑狼疮的遗传易感性之间的关系。同时,根据从医院收集的资料分析该位点基因多态性与SLE临床表型和实验室指征的关联。方法采用研究方法是病例对照研究,收集1387例SLE患者,患者来自于安徽省的2所三级甲等医院(安徽医科大学附属省立医院和安徽医科大学第一附属医院);收集健康对照2259例,用统一的调查问卷收集病例和对照的一般人口学资料和临床资料。利用Sequenom Mass ARRAY技术进行基因分型。应用SPSS 16.0进行统计分析。结果位点rs7574865在病例组GG、GT和TT的基因频率分别为35.11%、49.17%和15.72%;对照组基因型频率中分别为44.58%、44.35%和11.07%。在显性和隐性模型中均显示出差异有统计学意义(TT+GT vs GG:OR=1.487,95%CI:1.295-1.709);TT vs GG+GT:OR=1.510,95%CI:1.240-1.839);病例组和对照组中T和G的等位基因频率差异有统计学意义(P0.001)。显性模型下,位点rs7574865与盘状红斑的发生有关联,OR(95%CI)值为1.460(1.063-2.004)。但是,并未发现位点rs7574865与其余临床表型和实验室指标之间有关联(均有P0.05)。结论该人群STAT4位点rs7574865基因多态性与SLE遗传易感性有关,同时发现rs7574865基因多态性与盘状红斑有一定的关联,未发现与其他的临床表型和实验室指标有关联。研究二SLE患者PBMC中STAT4基因m RNA水平及其与IL23 m RNA和IL17 m RNA水平的相关性研究目的检测SLE患者和健康对照组PBMC中的STAT4,此外检测病例组IL17和IL23m RNA的水平,在基因表达的水平上探索STAT4基因与SLE的关联。分析STAT4基因表达分别与IL17、IL23基因表达的相关性。方法采集42例患者和33例对照的外周血,提取PBMC中的RNA,分别检测STAT4m RNA、IL17和IL23 m RNA的表达水平。采用Mann-Whitney U秩和检验比较各组间的STAT4表达是否存在差异。采用Spearman等级相关分析STAT4 m RNA表达与IL17 m RNA、IL23 m RNA表达之间的关联。统计软件是SPSS 16.0。结果42例病例组和33例对照组间PBMC中STAT4基因表达水平差异无统计学意义(Z=-1.516,P=0.130)。17例LN组和25例非LN组之间STAT4基因表达差异无统计学意义(Z=-0.243,P=0.808),活动组和非活动组STAT4基因表达差异无统计学意义(Z=-0.947,P=0.344)。临床表型中,发现皮疹和血管炎与STAT4基因表达相关(P0.05)。此外,研究发现,STAT4基因表达分别与IL17、IL23表达呈正相关(IL23:rs=0.741,P0.001;IL17:rs=0.486,P0.001)。结论未发现SLE病例组和对照组、活动组和非活动组、狼疮肾炎组和狼疮非肾炎组STAT4基因表达之间的差异。SLE患者中血管炎、皮疹与STAT4表达有关。SLE患者中STAT4基因表达与IL17、IL23基因表达呈正相关。
[Abstract]:To study the relationship between STAT4 gene polymorphism and clinical phenotype of systemic lupus erythematosus objective to study the relationship between STAT4 locus rs7574865 and genetic susceptibility of systemic lupus erythematosus. According to the data collected from the hospital, the association between the polymorphism of the locus gene and the clinical phenotype and laboratory indications of SLE was analyzed. Methods A case-control study was conducted in 1387 patients with SLE. The patients were from 2 Grade 3A hospitals in Anhui Province (provincial hospital affiliated to Anhui Medical University and the first affiliated Hospital of Anhui Medical University). 2259 healthy controls were collected. General demographics and clinical data of case and control were collected by uniform questionnaire. Genotyping was carried out by Sequenom Mass ARRAY technique. SPSS 16.0 was used for statistical analysis. Results the gene frequency of rs7574865 locus in GGG GT and TT was obtained in the case group. The frequency of genotypes in the control group was 44.58% and 11.07%, respectively. There were statistically significant differences in TT GT vs GG: 1.487-95CIW 1.295-1.709TT vs GG GTOR1. 51095 CIW 1.240-1.839; the allele frequencies of T and G were different in the case group and the control group. There is statistical significance in P0.001. under dominant model, There was a correlation between locus rs7574865 and the occurrence of discoid erythema. The value of ORY95CI was 1.460,1.063-2.004. However, there was no association between locus rs7574865 and other clinical phenotypic and laboratory indexes (all P 0.05). Conclusion the polymorphism of rs7574865 gene at STAT4 locus is associated with the genetic susceptibility of SLE in this population, but there is no correlation between the locus rs7574865 and other clinical phenotypic and laboratory indexes. It was also found that rs7574865 gene polymorphism was associated with discoid erythema. No association was found with other clinical phenotypes and laboratory markers. To study the relationship between m RNA level of STAT4 gene and IL23 m RNA and IL17 m RNA in PBMC of patients with second SLE objective to detect PBMC in SLE patients and healthy controls. STAT4, and the levels of IL17 and IL23m RNA in the case group, To explore the association between STAT4 gene and SLE at the level of gene expression, and to analyze the correlation between STAT4 gene expression and IL17 gene expression. Methods Peripheral blood samples were collected from 42 patients and 33 controls. The expression levels of STAT4m RNAs IL-17 and IL23 m RNA were detected. Mann-Whitney U rank sum test was used to compare the difference of STAT4 expression among the groups. Spearman rank correlation analysis was used to analyze the expression of STAT4 m RNA and IL17 m RNAl23 m RNA. Results there was no significant difference in the expression of STAT4 gene between 42 cases of PBMC and 33 cases of control group. There was no significant difference in the expression of STAT4 gene between 17 cases of LN group and 25 cases of non-LN group. There was no significant difference in STAT4 gene expression between the two groups. It was found that rashes and vasculitis were correlated with the expression of STAT4 gene (P 0.05). In addition, the expression of STAT4 gene was positively correlated with the expression of IL17: rsl 23, respectively. Conclusion there is no positive correlation between the expression of STAT4 gene and the expression of IL23: rssil 0.741P0.001IL17: rssil 0.486p0.001.Conclusion there are no cases of SLE, control group, active group and inactive group. The difference of STAT4 gene expression between lupus nephritis group and lupus non-glomerulonephritis group. There was a positive correlation between STAT4 gene expression and IL17 sil 23 gene expression in patients with STAT4.
【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】：R593.241

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