【作者】 王敏；

【导师】 叶冬青； 冷瑞雪；

【作者基本信息】 安徽医科大学 ， 流行病与卫生统计学， 2017， 硕士

【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(P<0.001)。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P>0.05)。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(P<0.05)。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,P<0.001;IL17:rs=0.486,P<0.001)。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。更多还原

【Abstract】 Part Ι Association study of STAT4 polymorphism with clinical features of systemic lupus erythematosusObjective To investigate the associations of the SNP(rs7574865)in STAT4 gene with susceptibility to SLE in a Chinese population.Morever,we also investigated whether this SNP was associated with the laboratory and clinical characteristics in SLE.Methods We conducted a case-control study and 1387 SLE patients were collected from two hospitals in Anhui Province(the First Affiliated Hospital and Anhui Provincial Hospital of Anhui Medical University).2259 controls was selected from healthy volunteers in the the First Affiliated Hospital of Anhui Medical University.The demographic data and clinical and laboratory characteristics were collected from the case and control by unified questionnaire.The Sequenom Mass ARRAY ? SNP detection technology were used to analyze the loci of STAT4 gene.All the data were analyzed by the SPSS 16.0 software.Results Genotypic frequencies for GG、GT and TT in SLE group were 35.11%、49.17% and 15.72%,respectively.The control group was 44.58%、44.35% and 11.07%,respectively.Significant differences were discovered both in the dominant model and recessive model(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).The allele frequencies of rs7574865 was statistically significant different between cases and controls(P<0.001).Clinical characteristics analysis showed a significant difference under a dominant model between patients with discoid rash and patients without this characteristics(OR=1.460,95% CI:1.063-2.004).We failed to find association of other clinical and laboratory features with rs7574865 in SLE patient(all P>0.05).Conclusion STAT4 gene polymorphism rs7574865 is associated with SLE susceptibility.The rs7574865 SNP was associated discoid rash.We failed to find any association of other clinical and laboratory features with rs7574865 in SLE patient.Part П Association study of STAT4 m RNA expression and IL17 m RNA、IL23m RNA in PBMC from patients with SLEObjective We detected the levels of STAT4,IL17 and IL23 m RNA of SLE patients and healthy controls,then explored the correlation between STAT4 gene and SLE at the level of gene expression.In addition,we analyzed the correlation between STAT4 m RNA and IL17 m RNA,IL23 m RNA expression,respectively.Methods We extracted the m RNA in PBMCs from 42 patients and 33 controls and detected STAT4 gene expression and IL17 and IL23 gene expression in patient.We used the Mann-Whitney U test to compare the STAT4 median m RNA between different groups.We used Spearman ’ s rank correlation to analyze the correlations between STAT4 m RNAand IL23 m RNA,IL17 m RNA.The software we used was SPSS 16.0.The probability level as <0.05 in two-tailed test was considered statistically significant.Results The STAT4 m RNA in PBMCs showed no significant difference between the 42 patients and 33 controls(Z=-1.516,P=0.130).We did not find significant difference between the 17 LN patients and 25 non-LN patients(Z=-0.243,P=0.808).No significant difference was found between the active patients and inactive patients(Z=-0.947,P=0.344).The STAT4 gene expression was significantly different between SLE patients with rash and vasculitis and patients without this characteristics(all P<0.05).Besides,there was a significant positive correlation between STAT4 gene expression and IL17,IL23 gene expression(IL23:rs=0.741,P<0.001;IL17: rs=0.486,P<0.001).Conclusion The STAT4 gene expression was not significantly different between the SLE group and the control group,the active group and the inactive group,the lupus nephritis group and the non-lupus nephritis group.The STAT4 gene expression was significantly different between SLE patients with vasculitis and rash.The STAT4 gene expression were positive correlated with IL17,IL23 gene expression.更多还原