ACE and PAI-1 gene polymorphisms in renal transplant recipients.

Extracellular matrix accumulation in renal tissue is the hallmark of progressive renal function loss in a variety of renal diseases, including renal allograft. Several studies have recently suggested a role for both the Renin-Angiotensin (RAS) and the Fibrinolytic System as modulators of extracellular matrix turnover. We investigated whether the genetic polymorphisms of the RAS components (insertion/deletion: I/D polymorphism of the Angiotensin I-converting enzyme (ACE) gene) and genetic polymorphisms of the Fibrinolytic System (insertion/deletion: 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene could have any influence on kidney graft survival in a recipient cohort. DNA was extracted from 130 adult recipients (mean age 49 years) who reached a minimum of one year GS (mean follow-up 5.25 +/- 3.64 years) after receiving a kidney graft in our center. A polymerase chain reaction (PCR) technique was utilized for ACE and PAI-1 genotyping. Our results have shown that: 1. actuarial graft survival at 5 and 10 years in recipients with ACE/II genotype was lightly higher although not reaching the statistical significance (p <0.4, p<0.06, respectively) than in recipients with ACE/DD genotype (88% vs 86% and 72% vs 55%, respectively); 2. actuarial graft survival at 5 and 10 years in recipients with PAI-1/4G5G genotype was higher than in recipients with PAI-1/4G4G and PAI-1/5G5G genotype (89% vs 81% vs 82% and 77% vs 45% vs 49%, respectively, with 4G5G genotype vs 4G4G genotype, p< 0.04); this observation indicated for 4G4G group a worse outcome in long term graft survival. In conclusion, the association of ACE/DD genotype with homozygosity in PAI-1 gene polymorphism seems to influence negatively the long-term kidney graft survival, thus suggesting a crucial role of a genetic environment in the progression of chronic kidney graft damage.