Association of HSP90B1 genetic polymorphisms with efficacy of glucocorticoids and improvement of HRQoL in systemic lupus erythematosus patients from Anhui Province.

IF 1.4 Q4 IMMUNOLOGY American journal of clinical and experimental immunology Pub Date : 2018-04-05 eCollection Date: 2018-01-01
Xiu-Xiu Sun, Su-Su Li, Man Zhang, Qiao-Mei Xie, Jian-Hua Xu, Sheng-Xiu Liu, Yuan-Yuan Gu, Fa-Ming Pan, Jin-Hui Tao, Sheng-Qian Xu, Shuang Liu, Jing Cai, De-Guang Wang, Long Qian, Chun-Huai Wang, Li Lian, Hui Xiao, Pei-Ling Chen, Chun-Mei Liang, You-Bing Fang, Qiang Zhou, Hai-Liang Huang, Hong Su, Hai-Feng Pan, Dong-Qing Ye, Yan-Feng Zou
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Abstract

Objective: 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). Method: 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. Results: 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 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 BH correction, 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 CTGGGACGTTC (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 HRQoL among SLE patients (P < 0.05). But no association existed after the correction of BH method (P > 0.05). Conclusions: 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.

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安徽省系统性红斑狼疮患者HSP90B1基因多态性与糖皮质激素疗效及HRQoL改善的关系
研究目的本研究旨在探讨安徽系统性红斑狼疮(SLE)患者 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)改善之间的关系。研究方法本研究共招募了 305 名系统性红斑狼疮患者。根据系统性红斑狼疮疾病活动指数(SLEDAI)的评分将这些患者分为两组(敏感组和不敏感组)。系统性红斑狼疮患者的 HRQoL 分别在基线和 12 周时通过 36 项简表健康调查(SF-36)进行评估。使用 HapMap 数据库和 Haploview 软件筛选 HSP90B1 基因标签单核苷酸多态性(SNPs)。采用基于假发现率(FDR)的Benjamini & Hochberg(BH)方法进行多重检验校正。结果共有 291 名患者被纳入最终数据分析,其中 14 名患者因失去随访而被排除。在这些患者中,160 名患者对 GCs 敏感,131 名患者对 GCs 不敏感。HSP90B1 基因的 12 个标记 SNPs 被选中。rs12426382多态性与GCs的疗效相关(显性模型:粗略OR=0.514,95% CI=0.321-0.824,P=0.006;调整OR=0.513,95% CI=0.317-0.831,P=0.007)。经 BH 校正后,rs12426382 多态性与 GCs 的疗效无关联(PBH =0.084)。在单倍型分析中,单倍型 CCCGAACATCCC(OR=2.273,95% CI=1.248-4.139,P=0.006)和 CTGGGACGTTC(OR=0.436,95% CI=0.208-0.916,P=0.025)与 GCs 的疗效有显著相关性。经 BH 方法校正后,CCCGAACATCCC 仍与 GCs 的疗效相关(PBH =0.048)。rs3794241、rs1165681、rs2722188、rs3794240 和 rs10861147 多态性与系统性红斑狼疮患者 HRQoL 的改善相关(P < 0.05)。但经 BH 方法校正后不存在相关性(P > 0.05)。结论本研究结果表明,HSP90B1 基因多态性可能与 GCs 的疗效有关,但与安徽系统性红斑狼疮患者 HRQoL 的改善无关。
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