Journal Article

Impact of plasminogen activator inhibitor-1 gene polymorphisms on  primary membranous nephropathy

Cheng-Hsu Chen, Kuo-Hsiung Shu, Mei-Chin Wen, Kuo-Jung Chen, Chi-Hung Cheng, Jong-Da Lian, Ming-Ju Wu, Tung-Min Yu and Fuu-Jen Tsai

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 10, pages 3166-3173
Published in print October 2008 | ISSN: 0931-0509
Published online May 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfn258
Impact of plasminogen activator inhibitor-1 gene polymorphisms on  primary membranous nephropathy

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Background. 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.

Methods. 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.

Results. 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).

Conclusions. 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.

Keywords: cardiovascular events; gene polymorphism; malignancy; plasminogen activator inhibitor; primary membranous nephropathy

Journal Article.  4581 words.  Illustrated.

Subjects: Nephrology

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