Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients

Details

Serval ID
serval:BIB_5454124B6E5B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients
Journal
Transplantation
Author(s)
Ferrari  P., Schroeder  V., Anderson  S., Kocovic  L., Vogt  B., Schiesser  D., Marti  H. P., Ganz  R., Frey  F. J., Kohler  H. P.
ISSN
0041-1337 (Print)
Publication state
Published
Issued date
10/2002
Volume
74
Number
8
Pages
1147-52
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct 27
Abstract
BACKGROUND: The mechanism of avascular osteonecrosis (AVN) is controversial. Besides an increased bone marrow pressure with reduced blood supply, an enhanced coagulation has been considered. We hypothesize that a genetic variant of the plasminogen activator inhibitor-1 (PAI-1) determines the risk of AVN in glucocorticoid-treated patients. METHODS: Genotyping for the 4G/5G PAI-1 polymorphism was performed in 228 glucocorticoid-treated renal transplant patients. AVN of the hip was present in 26 patients. Magnetic resonance imaging (MRI) of the hips was obtained in 81 of the remaining renal transplant patients without clinical symptoms of AVN. RESULTS: The presence of the homozygous 4G/4G PAI-1 genotype was higher in patients with AVN (60.3%) as compared with patients without either clinical (20.6%, P<0.007) or radiological signs of AVN (17.3%, P<0.002). The prevalence of AVN by genotype was 1.8% with the 5G/5G, 7.7% with the 5G/4G, and 30.3% with the 4G/4G alleles (P<0.001 vs. 5G/4G and 5G/5G). The prevalence of AVN increased with increasing body mass index (BMI) (P=0.04). The prevalence of AVN by genotype in subjects with persistent hyperparathyroidism was 4.2% with the 5G/5G, 15.2% with the 5G/4G, and 55.5% with the 4G/4G alleles (P<0.003 vs. 5G/4G and P<0.001 vs. 5G/5G). CONCLUSIONS: Hypofibrinolysis conferred by the 4G/4G PAI-1 gene variant is a major predisposing factor for AVN in renal transplant patients. The risk is particularly high in obese subjects or patients with persistent hyperparathyroidism. A prospective intervention study of early anticoagulation after renal transplantation is needed to assess whether glucocorticoid-associated AVN can be prevented.
Keywords
Adult Female Femur Head Necrosis/epidemiology/*genetics/pathology Genetic Predisposition to Disease/epidemiology Genotype Glucocorticoids/*therapeutic use Graft Rejection/*drug therapy/epidemiology/genetics Hip Joint/pathology Humans Kidney Failure, Chronic/epidemiology/genetics/surgery *Kidney Transplantation Magnetic Resonance Imaging Male Middle Aged Plasminogen Activator Inhibitor 1/*genetics Polymorphism, Genetic Prevalence Risk Factors Sex Distribution Transplantation, Homologous
Pubmed
Web of science
Create date
25/01/2008 14:03
Last modification date
20/08/2019 15:09
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