中文摘要
课题组前期发现热休克蛋白90(HSP90)和糖皮质激素受体(GR)基因单核苷酸多态性(SNP)在系统性红斑狼疮(SLE)治疗疗效预测中起着重要作用。同时预实验显示这些SNP在SLE发生中也可能起作用,但需进一步证实。拷贝数变异(CNV)是另一个重要遗传标记,HSP90和GR基因上CNV也可能和SLE发生和疗效有关,值得探讨。证据显示热休克蛋白70(HSP70)参与SLE发病,和HSP90共同参与糖皮质激素-GR通路,但中国人群当前少见其遗传变异和SLE关联报道。因此,本研究拟收集300例新发SLE患者和300例对照;对患者治疗24周,评定疗效;用SNaPshot/AccuCopyTM技术检测SNP/CNV;探讨HSP90、HSP70及GR基因遗传变异在SLE发生和治疗疗效预测中作用,本项目完成为开发SLE诊断和疗效预测基因试剂盒打下基础。
英文摘要
Our research group have discovered that heat shock protein 90 (HSP90) and glucocorticoid receptor (GR) gene single nucleotide polymorphism (SNP) play an important role in the treatment of systemic lupus erythematosus (SLE). Meanwhile, our pre-experimental results suggested that these SNPs may paly a certain role in the occurrence of SLE. But these findings need to be further explored. Copy number variation (CNV) is another important genetic marker, and the CNVs within HSP90 and GR gene may also be associated with the occurrence and therapeutic effect of glucocorticoid (GC) on SLE. This is a problem deserving of study. There is evidence that heat shock protein 70 (HSP70) is involved in the pathogenesis of SLE. HSP70 and HSP90 are jointly involved in the GC-GR pathway. But there are only a few reports on the association between the genetic variation (SNP/CNV) within HSP70 gene and SLE in Chinese population. Based on the aboved evidence, in the present study, 300 new-onset SLE patients and 300 controls will be enrolled. SLE patients will be treated for 24 weeks, and the therapeutic effect will be evaluated. SNaPshot and AccuCopyTM technologies are used to detect genetic variation (SNP/CNV). The purpose of the present study is to explore the role of genetic variation within HSP90, HSP70 and GR gene in the occurrence and treatment of SLE. The results of the resent study will lay a good foundation for the development of the SLE diagnosis and therapeutic effect prediction gene kit.
