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 ACE gene) and of the Fibrinolytic System (insertion/deletion: 4G/5G polymorphism of the PAI-1 gene) could have any influence on kidney graft survival (GS) 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 PCR technique was utilized for ACE and PAI-1 genotyping. Our results have shown that: 1. Actuarial GS at 10 years in recipients with ACE/II genotype was higher than in recipients with ACE/DD genotype (87% vs 54.5%, p <0.05); 2. Analyzing the ACE/DD group (n = 49) in relation to PAI-1 polymorphism, we observed that the actuarial GS of the 4G/5G genotype was higher than the homozygous conditions (4G/5G 81.9% vs 4G/4G 25.8% vs 5G/5G 27.3%; p <0.05); 3. ACE/DD genotype combined with homozygosity in the PAI-1 genotype is associated with a shorter kidney GS than ACE/II and ACE/ID genotypes (p <0.01). In conclusion, the association of ACE/DD genotype with homozygosity in PAI-1 gene polymorphism seems to in?uence negatively the long–term kidney GS, thus suggesting a crucial role of a genetic environment in the progression of chronic kidney graft damage.

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

SANTORI, GREGORIO;VALENTE, UMBERTO;
2011-01-01

Abstract

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 ACE gene) and of the Fibrinolytic System (insertion/deletion: 4G/5G polymorphism of the PAI-1 gene) could have any influence on kidney graft survival (GS) 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 PCR technique was utilized for ACE and PAI-1 genotyping. Our results have shown that: 1. Actuarial GS at 10 years in recipients with ACE/II genotype was higher than in recipients with ACE/DD genotype (87% vs 54.5%, p <0.05); 2. Analyzing the ACE/DD group (n = 49) in relation to PAI-1 polymorphism, we observed that the actuarial GS of the 4G/5G genotype was higher than the homozygous conditions (4G/5G 81.9% vs 4G/4G 25.8% vs 5G/5G 27.3%; p <0.05); 3. ACE/DD genotype combined with homozygosity in the PAI-1 genotype is associated with a shorter kidney GS than ACE/II and ACE/ID genotypes (p <0.01). In conclusion, the association of ACE/DD genotype with homozygosity in PAI-1 gene polymorphism seems to in?uence negatively the long–term kidney GS, thus suggesting a crucial role of a genetic environment in the progression of chronic kidney graft damage.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/260415
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