Plasminogen activator inhibitor-1 gene polymorphism 4G/4G genotype and lupus nephritis in Chinese patients.
Plasminogen activator inhibitor-1 gene polymorphism 4G/4G genotype and lupus nephritis in Chinese patients.
复制标题
中国患者纤溶酶原激活物抑制物1基因多态性4G/4G基因型与狼疮性肾炎
作者：
A. Wang;P. Poon;F. Lai;L. Yu;P. C. Choi;S. Lui;P. Li
背景
凝血和纤溶系统的异常调节可能在狼疮性肾炎肾小球损害中起重要作用。事实上，肾小球血栓形成经常发生在狼疮性肾炎和预测未来发展的肾小球硬化。在活动性狼疮肾炎的小鼠模型中，纤溶酶原激活物抑制剂-1（派-1）基因在整个肾脏中过度表达，包括肾小球内以及肾小管和血管中。派-1在狼疮性肾炎组织中的表达水平似乎与狼疮性肾炎的进展相关。最近，派-1基因的单碱基对插入/缺失4G/5G多态性已被鉴定并显示改变血浆派-1活性。因此，本研究旨在确定派-1基因4G/5G多态性与狼疮性肾炎的发展和严重程度的关联。
方法
采用聚合酶链反应（PCR）方法检测了118例系统性红斑狼疮（SLE）患者和103例年龄、性别相匹配的健康对照者的派-1基因多态性。派-1基因型结果与狼疮性肾炎的发展和严重程度的关系进行了研究。
结果
4G/5G等位基因频率在狼疮组为0.59/0.41，对照组为0.59/0.41（P = 1.000）。SLE伴肾炎组与不伴肾炎组的基因型分布差异无统计学意义。然而，与4G 5G和5G 5G基因型患者相比，4G 4G基因型狼疮肾炎患者的蛋白尿明显更重（5.0 vs 3.7 g/天; P = 0.023）。此外，73.3%的4G 4G患者的活动指数>或=8，而4G 5G和5G 5G患者的活动指数为37.3%（P = 0.003）。4G 4G组中51.7%的患者出现广泛坏死性病变，而4G 5G和5G 5G组中23.5%的患者出现广泛坏死性病变（P = 0.014）。4G 4G基因多态性与更高的肾炎活动性和更严重的坏死性病变的关联持续存在时，只有III类和IV类肾炎患者进行了研究。另一方面，派-1基因多态性与肾炎的慢性化之间没有显著关联。
结论
提示派-1基因4G/5G多态性与狼疮性肾炎的活动性有关，而与狼疮性肾炎的慢性化无关。4G 4G基因型的存在并不增加SLE或狼疮性肾炎的风险，但预示着更高的肾炎活动性和更广泛的坏死性病变的发展。
BACKGROUND
Abnormal regulation in the coagulation and fibrinolytic system may play an important role in mediating glomerular damage in lupus nephritis. Indeed, glomerular thrombosis occurs frequently in lupus nephritis and predicts the future development of glomerular sclerosis. In the murine model of active lupus nephritis, plasminogen activator inhibitor-1 (PAI-1) gene was overexpressed throughout the kidney, both within the glomeruli and also in tubules and vessels. The level of PAI-1 expression in the tissues appeared to correlate with the progression of lupus nephritis. Recently, a single base pair insertion/deletion 4G/5G polymorphism of the PAI-1 gene has been identified and shown to alter plasma PAI-1 activity. This study was therefore conducted to determine the association of the 4G/5G polymorphism of the PAI-1 gene with the development and severity of lupus nephritis.
METHODS
The PAI-1 gene polymorphism of 118 systemic lupus erythematosus (SLE) patients and 103 healthy controls who were gender and age matched was determined using standard polymerase chain reaction. PAI-1 genotype results were studied in relationship to the development and severity of lupus nephritis.
RESULTS
Allele frequencies of 4G/5G allele were 0.59/0.41 in lupus patients and 0.59/0.41 in controls (P = 1.000). No significant difference was noted in the genotype distribution between SLE patients with and without nephritis. However, lupus nephritis patients with the 4G4G genotype showed significantly heavier proteinuria (5.0 vs. 3.7 g/day; P = 0.023) when compared with patients with 4G5G and 5G5G genotypes. Also, 73.3% patients with 4G4G had an activity index > or =8 versus 37.3% patients with 4G5G and 5G5G (P = 0.003). Extensive necrotizing lesions were seen in 51.7% patients with 4G4G as compared with 23.5% patients with 4G5G and 5G5G (P = 0.014). The association of the 4G4G gene polymorphism with a higher nephritis activity and more severe necrotizing lesions persisted when only class III and class IV nephritis patients were studied. On the other hand, no significant association was noted between the PAI-1 gene polymorphism and the chronicity of the nephritis.
CONCLUSION
These findings suggest that the 4G/5G polymorphism of the PAI-1 gene is associated with the activity but not the chronicity of lupus nephritis. The presence of the 4G4G genotype does not increase the risk of developing SLE or lupus nephritis, but predicts the development of higher nephritis activity and more extensive necrotizing lesions.
狼疮性肾炎小鼠肾脏中肿瘤坏死因子和 IL-1 β 基因表达增加。
DOI：
--
发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boswell,JM;Yui,MA;Burt,DW;Kelley,VE
通讯作者：
Kelley,VE
狼疮性肾炎伴血栓形成和纤维蛋白溶解异常：ancrod 的作用。
DOI：
--
发表时间：
1985
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
Kant,KS;Pollak,VE;Dosekun,A;Glas-Greenwalt,P;Weiss,MA;Glueck,HI
通讯作者：
Glueck,HI
小鼠狼疮性肾炎肾组织中1型纤溶酶原激活剂抑制剂的表达。
影响因子：
19.6
作者：
Keeton,M;Ahn,C;Eguchi,Y;Burlingame,R;Loskutoff,DJ
通讯作者：
Loskutoff,DJ