糖皮质激素受体外显子9移码突变在狼疮肾炎发病及治疗中的意义

目的探讨下丘脑垂体肾上腺免疫轴稳定与否同狼疮肾炎（ＬＮ）发病间的关系。方法用放射免疫分析法及聚合酶链反应单链构象多态性（ＰＣＲＳＳＣＰ）、ＤＮＡ测序法分析观察３９例狼疮肾炎ＡＣＴＨ、皮质醇、糖皮质激素受体（ＧＲ）特性及其部分基因结构。结果ＡＣＴＨ、皮质醇在狼疮肾炎组及正常对照组无差别，ＧＲ位点在肾炎组明显低于正常组，但ＧＲ亲和性在两组之间无明显差别。３９例狼疮肾炎中有８例呈现ＧＲ基因外显子９单链构象多态性（ＳＳＣＰ）异常，其ＤＮＡ序列分析发现在ＧＲ基因的ｃＤＮＡ的第２４３９位点插入一个腺嘌呤核苷酸，此移码突变导致ＧＲ蛋白额外合成２０个氨基酸。结论ＧＲ异常可能与狼疮肾炎发病有关。

The phaseshift mutation in the glucocorticoid receptor gene causes resistance to gluocorticoidimmune regulation in lupus nephritis

Objective To study the relationship between endogenous glucocorticoid(GC) resistance and occurrence of lupus nephritis, and the molecular structure of GC receptor (GR) of the patients with lupus nephritis, which is responsible for mediating most known effects of GC at the cellular level. Methods The level of ACTH,GC,characteristic and part gene structure of GR in lupus nephritis and the control were observed. Results There was no difference in the level of ACTH,GC and the ligand affinity of GR between the patients and the control. GR number of mononuclear cell from lupus patients was lower than that of control, but which made no difference between the patients with different response to exogenous GC in clinic. Analysis of exon 9 of GR with polymerase chain reaction amplifiessingle strand coformation polymorphism (PCRSSCP) method showed that an abnormal band polymorphism in 8 patients from 39 lupus nephritis. DNA sequence analysis found one adenine inserting at 2439 base pair of GR gene. The phaseshift mutation caused additional 20 amino acids in GR protein translated by the abnormal gene. Conclusion The decrease of GR number and the molecular variation of GR could explain the GCresistance phenomenon and provide further evidence for abnormal GR in activation as a mechanism for the occurrence of lupus nephritis