Impact of plasminogen activator inhibitor-1 gene polymorphisms on primary membranous nephropathy.
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.
Chen
Cheng-Hsu
CH
Division of Nephrology, Taichung Veterans General Hospital, Taiwan.
Shu
Kuo-Hsiung
KH
Wen
Mei-Chin
MC
Chen
Kuo-Jung
KJ
Cheng
Chi-Hung
CH
Lian
Jong-Da
JD
Wu
Ming-Ju
MJ
Yu
Tung-Min
TM
Tsai
Fuu-Jen
FJ
D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics; D003404:Creatinine / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D003404:Creatinine