Association Study Of HSP90AA1 And HSP90AA2 Gene Polymorphisms With Sle Susceptibility,Glucocorticoids Efficacy And HRQoL Improvement

Objective To investigate whether the polymorphisms of HSP90AA2 gene is associated with the genetic susceptibility of systemic lupus erythematosus(SLE),the therapeutic efficacy of glucocorticoids(GCs)on SLE,and the improvement of health-related quality of life(HRQoL)in SLE patients.Methods A case-control study was performed and we collected 470 SLE patients and 470 normal controls from hospital.Genotyping of HSP90AA2 SNPs was carried out using Multiplex SNaPshot technique.Subsequently,444 SLE patients in the case group were followed up for 12 weeks(425 patients completed the follow-up and 19 patients was lost).The sensitivity of SLE patients to GCs was evaluated according to the SLE disease activity index(SLEDAI),and SLE patients were divided into GCs-sensitive group and GCs-insensitive group.HRQoL in SLE patients was assessed at baseline and week 12 using the SF-36 questionnaire.Changes of the score were used as an evaluation indicator of HRQoL improvement in SLE patients.Multiple comparison was corrected utilizing the Benjamini-Hochberg(BH)method.Results In the case control study,rs 18263 30 polymorphism showed association with SLE genetic susceptibility under dominant model(OR=0.738,95%CI=0.570-0.955,P=0.021)and additive model(OR=0.761,95%CI=0.616?0.940,P=0.011),but the association disappeared after multiple corrections(dominant model:PBH-0.063,additive model:PBH=0.063).The minor T allele of rs1826330 was associated with decreased SLE risk(OR=0.765,95%CI=0.621?0.941,P=0.011).In the haplotype analysis,TT haplotype of HSP90AA2 showed statistically significant difference in distribution between case and control group(OR=0.765,95%CI=0.621-0.941,P=0.011,PBH=0.033).In the follow-up study,no association was found between HSP90AA2 gene polymorphisms and GCs efficacy.But significant associations between rs6484340 polymorphism and improvement in physical function(dominant model:PBH=O.047,recessive model:PBH=0.029,additive model:PBH=0.026),role-physical(recessive model:PBH=0.041),mental health(dominant model PBH=0.047),physical component summary(dominant model:PBH=0.047,recessive model:PBH=0.029,additive model:PBH=0.026)and total score of SF-36(dominant model:PBH=0.047,recessive model:PBH=0.029,additive model:PBH=0.026)were revealed in the HRQoL analysisConclusion The results of this study demonstrated that HSP90AA2 gene polymorphisms may be associated with disease susceptibility and HRQoL improvement in Chinese population with SLEObjective To explore whether the polymorphisms of HSP90AA1 gene is associated with the genetic susceptibility of systemic lupus erythematosus(SLE)and the improvement of health-related quality of life(HRQoL)in SLE patientsMethods A total of 526 SLE patients and 526 normal controls were recruited to the case-control study.HapMap database and Haploview software were performed to select HSP90AA1 gene tag SNPs.Multiplex SNaPshot technique was used to genotype the SNPs.A 12-week follow-up was conducted in 489 SLE patients in the case group subsequently(470 patients completed the follow-up and 19 patients was lost).The SF-36 questionnaire was used to quantitatively evaluate the HRQoL of SLE patients at baseline and at week 12,respectively.Changes of the score in each domain were assessed to evaluate the improvements in HRQoL of SLE patients in Chinese population.Benjamini-Hochberg(BH)method was utilized to correct for multiple comparisonResults In the case-control study,no association was detected between HSP90AA1 gene polymorphisms and SLE susceptibility(P>0.05).While in the analysis of HRQoL,there was a significant association between rs11547523 polymorphism and improvement in role-physical(recessive model:P=0.028,additive model:P=0.017)and role-emotional(recessive model:P=0.017,additive model:P=0.008).The rs2298877 polymorphism was associated with improvement in role-physical(recessive model:P=0.025,additive model:P=0.026).The rs10873531 polymorphism was associated with improvement in role-physical(recessive model:P=0.014,additive model:P=0.021)and physical component summary(additive model:P=0.045)However,these associations disappeared after multiple corrections(all PBH>0.05).We also found a significant association between rs7160651 polymorphism and improvement in role-physical(recessive model:P=0.003,additive model:P=0.009),bodily pain(recessive model:P=0.019),physical component summary(recessive model:P=0.003,additive model:P=0.013)and the total score of SF-36(recessive model:P=0.028),and the associations with role-physical(recessive model:PBH-0.017)and physical component summary(recessive model:PBH=0.017)still existed after multiple corrections.Conclusion There is no association between HSP90AA1 gene polymorphisms and SLE susceptibility,but its polymorphism rs7160651 may affect the improvement of HRQoL in SLE patients.