Association Of HSP90B1 Gene Polymorphism With SLE Susceptibility And Treatment Efficacy

Part I Association of HSP90B1 gene polymorphisms with SLE SusceptibilityObjective To explore the association of HSP90B1 gene polymorphisms with susceptibility of systemic lupus erythematosus(SLE)in Chinese population.Methods We recruited 360 SLE patients from hospital as case group and selected 360 age-and sex-matched individuals without autoimmune diseases as control group.Multiplex SNa Pshot was used for genotyping.Benjamin & Hamburg(BH)method based on false discovery rate(FDR)standard was used for multiple testing correction.Results The rs1165681 polymorphism(crude OR=0.621,95%CI=0.450-0.856,P=0.004;adjusted OR=0.619,95%CI=0.449-0.855,P=0.004)was significantly associated with SLE risk reduction in dominant model,and the rs10778306 polymorphism(crude OR=0.568,95%CI=0.328-0.984,P=0.044;adjusted OR=0.570,95%CI=0.329-0.988,P=0.045)and the rs2722188 polymorphism(crude OR=0.227,95%CI=0.076-0.681,P=0.008;adjusted OR=0.227,95%CI=0.076-0.682,P=0.008)were significantly associated with SLE risk reduction in recessive model.After adjustment using BH method,genotype distribution of rs1165681 was statistical difference in two groups(PBH=0.044).Significant associations were found between four haplotypes of HSP90B1 gene CCATTAGGCAT(OR=0.323,95%CI=0.154-0.680,P=0.002),CCCTTAGGCAC(OR=1.324,95%CI=1.014-1.729,P=0.039),TCCCTAGTCGC(OR=0.465,95%CI=0.221-0.979,P=0.039)and TTCTCGGGCAT(OR=0.443,95%CI=0.224-0.875,P=0.016)and SLE risk.After adjustment using BH method,the frequency of CCATTAGGCAT distribution difference was statistically significant in two groups(PBH=0.028),but there were no statistical difference in other haplotypes frequency distributions(PBH >0.05).Conclusions HSP90B1 gene polymorphisms may be associated with the susceptibility of SLE in Chinese Han population.PART II Association of HSP90B1 genetic polymorphisms with Therapeutic Efficacy in SLE PatientsObjective The aim of this study was to investigate the associations between HSP90B1 gene polymorphisms and the efficacy of glucocorticoids(GCs)and the improvement of health-related quality of life(HRQo L)in Chinese population with SLE.Methods A total of 305 Chinese patients with SLE were recruited to the study.These patients were treated with GCs for 12 weeks and classified into two groups(sensitivity and insensitivity)according to the response to GCs measured by the scores on SLE disease activity index(SLEDAI).The HRQo L of SLE patients were evaluated by SF-36 at baseline and 12 weeks respectively.Hap Map database and Haploview softtware were used to select HSP90B1 gene tag SNPs.BH method based on FDR was utilized for multiple testing correction.Results A total of 291 patients were included in final data analysis with 14 patients excluded due to losing follow-up.Among these patients,160 patients were sensitive to GCs and 131 patients were insensitive to GCs.Twelve tag SNPs of HSP90B1 gene were selected.The rs12426382 polymorphism was associated with the efficacy of GCs(dominant model: crude OR=0.514,95%CI=0.321-0.824,P=0.006;adjusted OR=0.513,95%CI=0.317-0.831,P=0.007).After corrected by BH method,there was no association between rs12426382 polymorphism and efficacy of GCs(PBH=0.084).In haplotype analysis,the haplotype CCCGAACATCCC(OR=2.273,95%CI=1.248-4.139,P=0.006)and CTGGGACGTTCC(OR=0.436,95%CI=0.208-0.916,P=0.025)showed significant associations with the efficacy of GCs.After corrected by BH method,CCCGAACATCCC was still associated with the efficacy of GCs(PBH=0.048).The rs3794241,rs1165681,rs2722188,rs3794240 and rs10861147 polymorphisms were associated with the improvement of HRQo L among SLE patients(P<0.05).After corrected by BH method,no associations existed(PBH>0.05).Conclusions The results of this study demonstrated that HSP90B1 genetic polymorphisms might be associated with the efficacy of GCs,but without association with the improvement of HRQo L in Chinese population with SLE.