發(fā)布時間：2018-03-09 10:08

  本文選題：系統(tǒng)性紅斑狼瘡　切入點：易感性　出處：《安徽醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：第一部分 HSP90AB1基因多態(tài)性和SLE易感性的關(guān)聯(lián)研究目的探討HSP90AB1基因多態(tài)性與中國漢族人群系統(tǒng)性紅斑狼瘡(Systemic Lupus Erythematosus,SLE)發(fā)病之間的關(guān)系。方法采用病例對照的流行病學方法。收集278例來源于安徽醫(yī)科大學第一附屬醫(yī)院以及安徽醫(yī)科大學第二附屬醫(yī)院SLE患者,其中女257人,男21人,年齡為33.96±11.51歲。同期選擇年齡、性別、地區(qū)和民族與SLE患者相匹配的278例健康體檢者作為正常對照。利用Hap Map數(shù)據(jù)庫和Haploview軟件篩選出中國人群HSP90AB1基因標簽SNPs(Single Nucleotide Polymorphisms),采用Multiplex SNa Pshot技術(shù)對HSP90AB1基因中的rs9367190,rs13296進行基因分型。結(jié)果HSP90AB1基因rs9367190位點的三種基因型(CC、CA、AA)的頻率和等位基因C、A的頻率在SLE組與對照組分布差異有統(tǒng)計學意義(P0.05);遺傳分析模型中顯示,顯性模型(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)和隱性模型(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)與SLE易感性之間有關(guān)聯(lián);經(jīng)多重校正后,顯性模型(PBH=0.048)關(guān)聯(lián)仍然存在;而隱性模型(PBH=0.084)關(guān)聯(lián)消失。對于HSP90AB1基因rs13296位點,SLE組和對照組之間的基因型頻率(GG,GA和AA)和等位基因(G和A)頻率分布都無統(tǒng)計學差異(P0.05),并且顯性和隱性模型在多重校正前后都與SLE易感性無關(guān)聯(lián)(P0.05)。結(jié)論在中國人群中HSP90AB1基因多態(tài)性(rs9367190)可能和SLE易感性關(guān)聯(lián)。第二部分 SLE患者HSP90AB1基因多態(tài)性與GC療效及HRQo L改善的關(guān)聯(lián)研究目的分析中國人群系統(tǒng)性紅斑狼瘡(Systemic Lupus Erythematosus,SLE)患者HSP90AB1基因多態(tài)性是否與糖皮質(zhì)激素(Glucocorticoids,GC)治療SLE患者療效和健康相關(guān)生命質(zhì)量(Health Related Quality of Life,HRQo L)改善關(guān)聯(lián)。方法共有254名SLE患者完成了12周隨訪研究,有14例患者失訪。用SLE疾病活動指數(shù)(SLE Disease Activity Index,SLEDAI)的評分來評估GC的療效。根據(jù)對GC的敏感性,將SLE患者分為敏感和不敏感組。使用SF-36調(diào)查表對基線至12周的HRQo L進行定量評價。采用Multiplex SNa Pshot技術(shù)對HSP90AB1基因中的rs9367190,rs13296進行分型。結(jié)果SLE患者中rs9367190基因多態(tài)性(顯性模型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)與GC療效存在關(guān)聯(lián),而多重校正結(jié)果顯示不存在關(guān)聯(lián)(PBH=0.076)。單倍型分析中單倍型C/A與GC的療效存在關(guān)聯(lián)(OR=1.971,95%CI=1.135-3.425,P=0.015),經(jīng)多重校正后這種關(guān)聯(lián)仍存在(PBH=0.045)。遺傳分析模型中顯示,rs13296基因多態(tài)性與精神健康(MH)存在關(guān)聯(lián)(顯性模型:GA+AA vs.GG,0(-4.00-4.00)vs0(-4.00-8.00),P=0.049),經(jīng)多重校正后顯示rs13296基因多態(tài)性與HRQo L改善無關(guān)聯(lián)。結(jié)論中國人群中HSP90AB1基因rs9367190位點多態(tài)性可能與SLE患者GC的療效有關(guān)。
[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 鹵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.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.241

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