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Association Of HSP90AB1 Gene Polymorphism With SLE Susceptibility,Treatment Efficacy And HRQoL Improvement

Posted on:2018-09-13Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y GuFull Text:PDF
GTID:2334330515952873Subject:Epidemiology and Health Statistics
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Part I Association of HSP90AB1 Gene Polymorphism with SLE susceptibilityObjective To investigate the association of HSP90AB1 gene polymorphism with systemic lupus erythematosus(SLE)in Chinese Han population.Methods A case-control study was conducted.Two hundred and seventy eight cases of SLE patients were collected from the First Affiliated Hospital of Anhui Medical University and the Second Affiliated Hospital of Anhui Medical University,including 257 females and 21 males,aged 33.96 ± 11.51 years.At the same time,we selected 278 healthy subjects who matched age,sex,region and nationality with SLE patients as normal control.The single nucleotide polymorphisms(SNPs)of HSP90AB1 gene were screened by Haploview and Hap Map software.Genotypes of rs9367190 and rs13296 in HSP90AB1 were analyzed by multiplex SNa Pshot.Results The frequencies of three genotypes(CC,CA,and AA)and allele C,A in the rs9061190 locus of HSP90AB1 gene were significantly different between SLE group and control group(P<0.05).In the genetic analysis model,the dominant model(CC vs.CA + AA: OR=0.648,95%CI=0.464-0.906,P=0.011;ORadjust=0.649,95% CI=0.464-0.908,Padjust=0.012)and the recessive model(CC + CA vs.AA: OR=0.509,95%CI=0.266-0.976,P=0.042;ORadjust=0.509,95%CI=0.265-0.977,Padjust=0.042)were associated with SLE susceptibility.After multiple corrections,the association in dominant model(PBH = 0.048)still exists and the association in recessive model(PBH = 0.084)disappears.For HSP90AB1 gene rs13296 locus,the genotypes frequencies(GG,GA and AA)and the allele(G and A)frequencies were not statistically significantion different between SLE group and the control group(P>0.05),and the dominant and recessive models were not associated with SLE susceptibility(P>0.05)before or after multiple corrections.Conclusion HSP90AB1 gene polymorphism(rs9367190)may be associated with SLE susceptibility in Chinese population.PART II Relationship Between HSP90AB1 Gene Polymorphism and GC Efficacy and HRQo L Improvement in SLE PatientsObjective The aim of this study was to investigate whether HSP90AB1 gene polymorphism in patients with systemic lupus erythematosus(SLE)is associated with glucocorticoid(GC)efficacy and health-related quality of life(HRQo L)in Chinese population.Methods A total of 254 patients with SLE completed a 12-week follow-up study,in addition,14 patients were lost to follow-up.The efficacy of GC was evaluated by the SLE Disease Activity Index(SLEDAI)score.According to the sensitivity of GCS,SLE patients were divided into sensitive and insensitive groups.HRQo L from baseline to 12 weeks was quantified by the SF-36 questionnaire.The HSP90AB1 gene rs9367190 and rs13296 were typed by Multiplex SNa Pshot.Results The rs9367190 gene polymorphism(dominant model: CA + AA vs.CC: OR=0.562,95%CI=0.341-0.926,P=0.024;ORadjust=0.536,95%CI=0.319-0.902,P=0.019)was associated with GC efficacy in SLE patients,whereas multiple correction results showed no association(PBH = 0.076).Haplotype C/A was associated with GC efficacy in haplotype analysis(OR=1.971,95%CI=1.135-3.425,P=0.015).This association was still present after multiple corrections(PBH = 0.045).Genetic analysis model showed that rs13296 gene polymorphism was associated with mental health(MH)(dominant model: GA + AA vs.GG,0(-4.00-4.00)vs 0(-4.00-8.00),P=0.049).After multiple corrections showed that rs13296 gene polymorphism was not associated with the improvement of HRQo L.Conclusion The rs9367190 polymorphism of HSP90AB1 gene may be related to the efficacy of GC in SLE patients in Chinese population.
Keywords/Search Tags:systemic lupus erythematosus, susceptibility, HSP90AB1, polymorphism, glucocorticoid, HSP90AB1, health related quality of life, gene polymorphism
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