HSP90AB1基因多态性与SLE易感性、治疗疗效及HRQoL改善的关联研究

发布时间：2018-03-09 10:08

本文选题：系统性红斑狼疮　切入点：易感性　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：第一部分 HSP90AB1基因多态性和SLE易感性的关联研究目的探讨HSP90AB1基因多态性与中国汉族人群系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)发病之间的关系。方法采用病例对照的流行病学方法。收集278例来源于安徽医科大学第一附属医院以及安徽医科大学第二附属医院SLE患者,其中女257人,男21人,年龄为33.96±11.51岁。同期选择年龄、性别、地区和民族与SLE患者相匹配的278例健康体检者作为正常对照。利用Hap Map数据库和Haploview软件筛选出中国人群HSP90AB1基因标签SNPs(Single Nucleotide Polymorphisms),采用Multiplex SNa Pshot技术对HSP90AB1基因中的rs9367190,rs13296进行基因分型。结果HSP90AB1基因rs9367190位点的三种基因型(CC、CA、AA)的频率和等位基因C、A的频率在SLE组与对照组分布差异有统计学意义(P0.05);遗传分析模型中显示,显性模型(CC vs.CA+AA:OR=0.648,95%CI=0.464-0.906,P=0.011;OR校正=0.649,95%CI=0.464-0.908,P校正=0.012)和隐性模型(CC+CA vs.AA:OR=0.509,95%CI=0.266-0.976,P=0.042;OR校正=0.509,95%CI=0.265-0.977,P校正=0.042)与SLE易感性之间有关联;经多重校正后,显性模型(PBH=0.048)关联仍然存在;而隐性模型(PBH=0.084)关联消失。对于HSP90AB1基因rs13296位点,SLE组和对照组之间的基因型频率(GG,GA和AA)和等位基因(G和A)频率分布都无统计学差异(P0.05),并且显性和隐性模型在多重校正前后都与SLE易感性无关联(P0.05)。结论在中国人群中HSP90AB1基因多态性(rs9367190)可能和SLE易感性关联。第二部分 SLE患者HSP90AB1基因多态性与GC疗效及HRQo L改善的关联研究目的分析中国人群系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)患者HSP90AB1基因多态性是否与糖皮质激素(Glucocorticoids,GC)治疗SLE患者疗效和健康相关生命质量(Health Related Quality of Life,HRQo L)改善关联。方法共有254名SLE患者完成了12周随访研究,有14例患者失访。用SLE疾病活动指数(SLE Disease Activity Index,SLEDAI)的评分来评估GC的疗效。根据对GC的敏感性,将SLE患者分为敏感和不敏感组。使用SF-36调查表对基线至12周的HRQo L进行定量评价。采用Multiplex SNa Pshot技术对HSP90AB1基因中的rs9367190,rs13296进行分型。结果SLE患者中rs9367190基因多态性(显性模型CA+AA vs.CC:OR=0.562,95%CI=0.341-0.926,P=0.024;OR校正=0.536,95%CI=0.319-0.902,P校正=0.019)与GC疗效存在关联,而多重校正结果显示不存在关联(PBH=0.076)。单倍型分析中单倍型C/A与GC的疗效存在关联(OR=1.971,95%CI=1.135-3.425,P=0.015),经多重校正后这种关联仍存在(PBH=0.045)。遗传分析模型中显示,rs13296基因多态性与精神健康(MH)存在关联(显性模型:GA+AA vs.GG,0(-4.00-4.00)vs0(-4.00-8.00),P=0.049),经多重校正后显示rs13296基因多态性与HRQo L改善无关联。结论中国人群中HSP90AB1基因rs9367190位点多态性可能与SLE患者GC的疗效有关。
[Abstract]:Part I the association between HSP90AB1 gene polymorphism and SLE susceptibility objective to investigate the relationship between HSP90AB1 gene polymorphism and the incidence of systemic lupus erythematosus in Chinese Han population. Methods: a total of 278 SLE patients from the first affiliated Hospital of Anhui Medical University and the second affiliated Hospital of Anhui Medical University were collected. There were 257 females and 21 males, aged 33.96 卤11.51 years. Hap Map database and Haploview software were used to screen HSP90AB1 gene tag SNPs(Single Nucleotide Polymorphis msg of Chinese population, and Multiplex SNa Pshot technique was used to base the gene rs9367190U rs13296 in HSP90AB1 gene. Results the frequency and allele frequency of rs9367190 locus of HSP90AB1 gene were significantly different between SLE group and control group (P 0.05). The dominant model CC vs.CA: 0.64895 CIQ 0.464-0.906 P0.011OR correction 0.649-95CII 0.464-0.908P correction 0.012) and the recessive model CC CA vs.AAOR-0.509C95 / CI0.266-0.976P0.042OR correction / 0.50995CIA 0.265-0.977CIA / 0.265-0.977CIA / 0.265-0.977CIA / P = 0.265-0.977C / P = 0.265-0.977P = 0.265-0.977C = 0.265-0.977C = 0.265-0.977P = 0.265-0.977C / P = 0.265-0.977C / P = 0.265-0.977C / P = 0.265-0.977P = 0.265-0.977a) respectively. For HSP90AB1 gene rs13296 locus, there was no significant difference in genotype frequencies between rs13296 locus and control group (P 0.05), and the dominant and recessive models were corrected by multiple recalculations (P < 0. 05), but no significant difference was found in the genotype frequency distribution between rs13296 locus and control group (P < 0. 05), and there was no significant difference in allele G and G (P 0. 05) between HSP90AB1 gene rs13296 locus group and control group. Conclusion the polymorphism of HSP90AB1 gene rs9367190 may be associated with the susceptibility of SLE in Chinese population. Part 2 of the study on the association of HSP90AB1 gene polymorphism with the efficacy of GC and the improvement of HRQo L in SLE patients objective to analyze the relationship between the polymorphism of HSP90AB1 gene and the susceptibility of SLE. Whether the polymorphism of HSP90AB1 gene in patients with systemic lupus erythematosus (SLE) was associated with the effect of glucocorticoid therapy on SLE and the improvement of health related quality of life (QOL). Methods A total of 254 SLE patients were followed up for 12 weeks. The efficacy of GC was evaluated with the SLE Disease Activity Index (SLEDAI) score, according to the sensitivity to GC. SLE patients were divided into sensitive and insensitive groups. HRQo L from baseline to 12 weeks was quantitatively evaluated by SF-36 questionnaire. Multiplex SNa Pshot technique was used to type the HSP90AB1 gene rs9367190 rs13296. Results the rs9367190 gene polymorphism in SLE patients was dominant (P < 0.05). Model CA AA vs.CC: ORO 0.56295 CIQ 0.341-0.926P0.024OR correction 0.536C 95CII 0.319-0.902P correction 0.019) were associated with GC efficacy. In haplotype analysis, there was a correlation between the efficacy of haplotype C / A and GC. There was a significant association (dominance model GA AA vs.GGG 0C -4.00-4.00 vs0 -4.00-8.00). After multiple correction, there was no association between the polymorphism of rs13296 gene and the improvement of HRQo L. ConclusionThe polymorphism of rs9367190 locus of HSP90AB1 gene may be related to the curative effect of GC in SLE patients in Chinese population.
【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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