Sun Xiu-Xiu, Li Su-Su, Zhang Man, Xie Qiao-Mei, Xu Jian-Hua, Liu Sheng-Xiu, Gu Yuan-Yuan, Pan Fa-Ming, Tao Jin-Hui, Xu Sheng-Qian, Liu Shuang, Cai Jing, Wang De-Guang, Qian Long, Wang Chun-Huai, Lian Li, Xiao Hui, Chen Pei-Ling, Liang Chun-Mei, Fang You-Bing, Zhou Qiang, Huang Hai-Liang, Su Hong, Pan Hai-Feng, Ye Dong-Qing, Zou Yan-Feng
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University Hefei 230032, Anhui, China.
The Key Laboratory of Major Autoimmune Diseases Hefei 230032, Anhui, China.
Am J Clin Exp Immunol. 2018 Apr 5;7(2):27-39. eCollection 2018.
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 (HRQoL) in Anhui patients with systemic lupus erythematosus (SLE). A total of 305 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 HRQoL of SLE patients were evaluated by 36-item Short Form Health Survey (SF-36) at baseline and 12 weeks respectively. HapMap database and Haploview software were used to select HSP90B1 gene tag single nucleotide polymorphisms (SNPs). Benjamini & Hochberg (BH) method based on false discovery rate (FDR) was used for multiple testing correction. A total of 291 patients were included in final data analysis with 14 patients excluded due to loss to 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 =0.514, 95% =0.321-0.824, =0.006; adjusted =0.513, 95% =0.317-0.831, =0.007). After BH correction, there was no association between rs12426382 polymorphism and efficacy of GCs ( =0.084). In haplotype analysis, the haplotype CCCGAACATCCC (=2.273, 95% =1.248-4.139, =0.006) and CTGGGACGTTC (=0.436, 95% =0.208-0.916, =0.025) showed significant associations with the efficacy of GCs. After corrected by BH method, CCCGAACATCCC was still associated with the efficacy of GCs ( =0.048). The rs3794241, rs1165681, rs2722188, rs3794240 and rs10861147 polymorphisms were associated with the improvement of HRQoL among SLE patients ( < 0.05). But no association existed after the correction of BH method ( > 0.05). The results of this study demonstrated that HSP90B1 genetic polymorphisms might be associated with the efficacy of GCs, but not associated with the improvement of HRQoL in Anhui population with SLE.
本研究旨在探讨安徽系统性红斑狼疮(SLE)患者中热休克蛋白90β1(HSP90B1)基因多态性与糖皮质激素(GCs)疗效及健康相关生活质量(HRQoL)改善之间的关联。共招募了305例SLE患者参与本研究。这些患者接受GCs治疗12周,并根据SLE疾病活动指数(SLEDAI)评分所测得的对GCs的反应分为两组(敏感组和不敏感组)。分别在基线和12周时通过36项简明健康调查(SF - 36)对SLE患者的HRQoL进行评估。使用HapMap数据库和Haploview软件选择HSP90B1基因标签单核苷酸多态性(SNPs)。采用基于错误发现率(FDR)的Benjamini & Hochberg(BH)方法进行多重检验校正。最终数据分析纳入了291例患者,14例因失访被排除。在这些患者中,160例对GCs敏感,131例对GCs不敏感。选择了HSP90B1基因的12个标签SNPs。rs12426382多态性与GCs疗效相关(显性模型:粗比值 = 0.514,95%可信区间 = 0.321 - 0.824,P = 0.006;校正后比值 = 0.513,95%可信区间 = 0.317 - 0.831,P = 0.007)。经BH校正后,rs12426382多态性与GCs疗效无关联(P = 0.084)。在单倍型分析中,单倍型CCCGAACATCCC(P = 2.273,95%可信区间 = 1.248 - 4.139,P = 0.006)和CTGGGACGTTC(P = 0.436,95%可信区间 = 0.208 - 0.916,P = 0.025)与GCs疗效显著相关。经BH方法校正后,CCCGAACATCCC仍与GCs疗效相关(P = 0.048)。rs3794241、rs1165681、rs2722188、rs3794240和rs10861147多态性与SLE患者HRQoL的改善相关(P < 0.05)。但经BH方法校正后无关联(P > 0.05)。本研究结果表明,HSP90B1基因多态性可能与安徽SLE人群中GCs的疗效相关,但与HRQoL的改善无关。