Chen Cheng-Hsu, Shu Kuo-Hsiung, Wen Mei-Chin, Chen Kuo-Jung, Cheng Chi-Hung, Lian Jong-Da, Wu Ming-Ju, Yu Tung-Min, Tsai Fuu-Jen
Division of Nephrology, Taichung Veterans General Hospital, Taiwan.
Nephrol Dial Transplant. 2008 Oct;23(10):3166-73. doi: 10.1093/ndt/gfn258. Epub 2008 May 21.
Idiopathic membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults, and 25% of MN patients proceed to end-stage renal disease. Plasminogen activator inhibitor type 1 (PAI-1) activity plays an important role in renal fibrosis. The objective of this study was to clarify the relationship between PAI-1 gene polymorphisms and the progression of MN-associated pathologies.
We recruited a cohort of 104 biopsy-diagnosed MN patients and 142 healthy subjects that served as controls. Genotyping of PAI-1 gene polymorphisms was performed using allele-specific polymerase chain reaction methods. We then analysed associations between PAI-1 gene 4G/5G polymorphisms and clinical manifestations and progression of MN.
The genotype distribution had no effect on the development of MN. The last measured creatinine clearance in MN patients having the 4G/4G genotype was significantly lower than in patients having the 4G/5G or 5G/5G genotypes (43.6 +/- 33.6, 55.8 +/- 44.3 and 73.3 +/- 29.8 ml/min, respectively, P = 0.008). Coronary artery diseases were more prevalent in patients having the 4G5G (14/32%) and 4G4G genotypes (4/11%) than in those having the 5G5G genotype (1/5%, P = 0.008). Peripheral vascular events were more prevalent in patients having the 4G5G (18/41%) and 4G4G (6/16%) genotypes than in those having the 5G5G genotype (3/14%, P = 0.021). Disease progression occurred more frequently in patients having the 4G4G (20/53%) and 4G5G (25/57%) genotypes compared with those having the 5G5G genotype (5/23%, P = 0.026).
The presence of the 4G allele was associated with renal deterioration and increased cardiovascular as well as other vascular events in MN patients. These findings should prompt specific considerations for the treatment of MN in patients having the 4G4G genotype.
特发性膜性肾病（MN）是成人肾病综合征最常见的病因之一，25%的MN患者会发展为终末期肾病。纤溶酶原激活物抑制剂1（PAI-1）活性在肾纤维化中起重要作用。本研究的目的是阐明PAI-1基因多态性与MN相关病变进展之间的关系。
我们招募了一组104例经活检确诊的MN患者和142例健康受试者作为对照。使用等位基因特异性聚合酶链反应方法对PAI-1基因多态性进行基因分型。然后我们分析了PAI-1基因4G/5G多态性与MN的临床表现及进展之间的关联。
基因型分布对MN的发生没有影响。4G/4G基因型的MN患者最后一次测得的肌酐清除率显著低于4G/5G或5G/5G基因型的患者（分别为43.6±33.6、55.8±44.3和73.3±29.8 ml/分钟，P = 0.008）。4G5G（14/32%）和4G4G基因型（4/11%）的患者中冠状动脉疾病比5G5G基因型（1/5%）的患者更常见（P = 0.008）。4G5G（18/41%）和4G4G（6/16%）基因型的患者中周围血管事件比5G5G基因型（3/14%）的患者更常见（P = 0.021）。与5G5G基因型（5/23%）的患者相比，4G4G（20/53%）和4G5G（25/57%）基因型的患者疾病进展更频繁（P = 0.026）。
4G等位基因的存在与MN患者的肾脏恶化、心血管及其他血管事件增加有关。这些发现应促使对4G4G基因型患者的MN治疗进行特殊考虑。
