Association Study Of HSP70 Gene Polymorphism With Susceptibility And Glucocorticoids Efficacy Of Systemic Lupus Erythematosus

Part Ⅰ Association of HSP70 gene polymorphisms with systemic lupus erythematosus SusceptibilityObjective To investigate the association of HSP70 gene polymorphisms with systemic lupus erythematosus（SLE）susceptibility in Chinese Han population.Methods A totall of 499 SLE patients and 499 healthy controls were collected in this case-control study.All of the patients and controls were recruited from the department of Rheumatology and Immunology and the department of Health Examination Center at the first and the second affiliated hospitals of anhui medical university respectively.Hap Map database and Haploview software were used to select HSP70 gene tag SNPs,improved Multiple Ligase Detection Reaction（i MLDR）was used to genotyped the SNPs.SPSS 16.0 and SAS 9.0 were used for statistical analysis,Benjamin&Hamburg（BH）method which based on false discovery rate（FDR）standard was utilized for multiple corrections.Results The rs2075800 polymorphism was significantly associated with SLE susceptibility in dominant model（crude OR=1.436,95%CI=1.113-1.854,P=0.005;adjusted OR=1.437,95%CI=1.113-1.855,P=0.005）;the rs2075799 polymorphism was significantly associated with SLE susceptibility in recessive model（crude OR=0.521,95%CI=0.275-0.989,P=0.046;adjusted OR=0.523,95%CI=0.275-0.992,P=0.047）;the rs2722188 polymorphism was significantly associated with SLE susceptibility in CC vs GG model（crude OR=0.600,95%CI=0.375-0.961,P=0.034;adjusted OR=0.601,95%CI=0.375-0.962,P=0.034）;the rs2075799（crude OR=0.511,95%CI=0.268-0.975,P=0.042;adjusted OR=0.512,95%CI=0.268-0.978,P=0.043）and rs2075800（crude OR=1.602,95%CI=1.072-2.394,P=0.022;adjusted OR=1.602,95%CI=1.072-2.395,P=0.022）polymorphisms were significantly associated with SLE susceptibility in TT vs CC model;the rs2075800 polymorphism was significantly associated with SLE susceptibility in TC vs CC model（OR=1.395,95%CI=1.067-1.824,P=0.015;adjusted OR=1.396,95%CI=1.067-1.826,P=0.015）.After the adjustment of BH method,the rs2075800 polymorphism was still associated with SLE susceptibility under the dominant model,TT vs CC model and TC vs CC model(P_BH=0.020,P_BH=0.029,P_BH=0.029,respectively).The results of haplotype analysis showing that CAGCCTT haplotype was associated with the increased risk of SLE（OR=1.234,95%CI=1.024-1.488,P=0.027）,after correcting for BH analysis,the statistical difference was nonexistent(P_BH=0.162).Conclusions The TT+TC,TT and TC genotypes of rs2075800 in SLE patients were statistically different from the healthy controls,suggesting that the polymorphism of HSP70 gene might be associated with susceptibility to SLE in Chinese Han population.PART Ⅱ Association of HSP70 genetic polymorphisms with GCs efficacy in systemic lupus erythematosus patientsObjective The aim of this study was to explore whether single nucleotide polymorphisms（SNPs）within HSP70 gene affect the efficacy of GCs treatment in Chinese Han systemic lupus erythematosus（SLE）patients.Methods In this prospective study,four hundred and sixty-eight SLE patients who met the inclusion criteria were followed up for 12 weeks.SLE disease activity index（SLEDAI）was used to assess the response of SLE patients to GCs treatment,and divided these patients into the GCs sensitive group and the GCs insensitive group according to the SLEDAI score results.The SF-36 was used to evaluate the health-related quality of life（HRQOL）of SLE patients.Hap Map database and Haploview software were used to select HSP70 gene tag SNPs,improved Multiple Ligase Detection Reaction（i MLDR）was used to genotyped the SNPs.SPSS 16.0 and Benjamin & Hamburg（BH）method which based on false discovery rate（FDR）standard were utilized for statistic analysis and multiple testing correction,respectively.Results A total of 449 SLE patients finished the 12-week follow-up and included in final data analysis,19 patients were lost to follow-up.Of all the patients who completed the follow-up,261 were included in the GCs sensitive group and 188 were included in the GCs insensitive group.According to the results of logistics regression,we found that the rs2227956 polymorphism was associated with the efficacy of GCs（dominant model:crude OR=1.449,95%CI=0.979-2.144,P=0.064;adjusted OR=1.527,95%CI=1.018-2.291,P=0.041）.After the adjustment of BH method,this association no longer exists(P_BH=0.287).In haplotype analysis,we found that the haplotype of HSP70 gene was not associated with the therapeutic effect of GCs.Nonparametric test indicated that,the polymorphism of rs2227956 was associated with the improvement of the role emotional（P=0.029）,the polymorphism of rs2075800 was associated with improvement of the general health（P=0.036）,and the polymorphism of rs2075799 was associated with improvement of mental health（P=0.004）.After adjusting for BH,the association between rs2075799 polymorphism and mental health improvement still remained(P_BH=0.044).Conclusions HSP70 gene polymorphism was not associated with the therapeutic effect of GCs in Chinese Han SLE patients,but it might be associated with the mental health status of SLE patients.