Copy number variations and polymorphisms in HSP90AB1 and risk of systemic lupus erythematosus and efficacy of glucocorticoids.

Man Zhang,Wenbiao Hu,Jian Cheng,Shengxiu Liu,Yangfan Chen,Long Qian,Chunmei Liang,Zhiwei Xu,Faming Pan,Qiuyue Lou,Hong Su,Hailiang Huang,Shuang Liu,Chunhuai Wang,Qiaomei Xie,Shengqian Xu,Jing Cai,Shunwei Huang,Peiling Chen,Yuzhou Zhang,Yanfeng Zou,Yuxiang Gu ,Jin‐Hui Tao ,Hai‐Feng Pan

doi:10.1111/jcmm.14410

Abstract

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single‐nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health‐related quality of life (HRQoL) was also measured by SF‐36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (P BH = 0.039), and this association was more pronounced in the female subgroup (P BH = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role‐emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs.

Highlights

Systemic lupus erythematosus (SLE) is a systematic autoimmune inflammatory disease with a varying clinical manifestation, and its incidence is much higher in women than in men (>8:1).[1,2] In clinical practice, a first‐line therapy for SLE patients is long‐term use of glucocorticoids (GCs), which exert their biological effects after combining with glucocorticoid receptor (GR)
It is well known that SLE is a polygenic disease, a considerable number of loci have been confirmed to be associated with SLE through genome‐wide association studies of single‐nucleotide polymorphism (SNP) over the past several years
Recent studies have found that genetic factors may play a role in the prognosis judgement, but such studies are mainly related to cancer

Summary

| INTRODUCTION

Systemic lupus erythematosus (SLE) is a systematic autoimmune inflammatory disease with a varying clinical manifestation, and its incidence is much higher in women than in men (>8:1).[1,2] In clinical practice, a first‐line therapy for SLE patients is long‐term use of glucocorticoids (GCs), which exert their biological effects after combining with glucocorticoid receptor (GR). HSP90 has two major cytosolic isoforms, respectively HSP90AA1 and HSP90AB1 They play different roles in differentiation and development, as well as in response to heat stress and other environmental stimulations.[10,11]. We have reported previously that genetic polymorphisms of HSP90AA1 had an influence on the response of SLE patients to GCs treatment.[12]. This study was to confirm the role of HSP90AB1 gene CNVs with the risk of SLE and efficacy of GCs. Our previous case‐control research[16] has investigated the association of polymorphisms in the HSP90AB1 gene with susceptibility to SLE. We sought to further explore the association between HSP90AB1 gene polymorphisms and GCs efficacy. The relationship of the improvement in health‐related quality of life (HRQoL) with HSP90AB1 gene CNVs and polymorphisms was evaluated

| MATERIALS AND METHODS

Findings

| DISCUSSION