NDT Advance Access published online on May 21, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn258
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Impact of plasminogen activator inhibitor-1 gene polymorphisms on primary membranous nephropathy
1 Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital 2 Institute of Clinical Medicine, China Medical University 3 Department of Biotechnology, Hung Kuang University 4 Division of Nephrology, Chung Shan Medical University Hospital 5 Department of Life Science, Tunghai University 6 Department of Pathology, Taichung Veterans General Hospital 7 School of Medicine, National Yang-Ming University, Taipei 8 Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan
Correspondence and offprint requests to: Cheng-Hsu Chen, Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. Tel: +886-4-23592525; Fax: +886-4-23594980; E-mail: cschen920{at}yahoo.com, cschen{at}vghtc.gov.tw
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Abstract |
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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
Received for publication: 30. 8.07
Accepted in revised form: 15. 4.08