부산대학교 도서관

Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles in hypertension and progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients (47 males and 35 females; mean age 34.87±11.22 years). One hundred healthy subjects (54 males and 46 females; mean age 35.54±10.26 years) were also investigated for AGT polymorphism, and 80 healthy subjects (45 males and 35 females; mean age 36.54±12.41) for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction sequence-specific primers, and polymerase chain reaction followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than those without CAD. (P <0.05 and P <0.001, respectively) Presence of the MT genotype was significantly associated with CAD, and this genotype introduced a 3.5-fold risk of CAD compared with the MM genotype ( P <0.05; 95% confidence interval: 1.21–10.20). The transplant recipients with CAD also had significantly lower frequencies of the 5G/5G genotype and the 5G allele than those without CAD ( P <0.001 and P <0.05, respectively). Presence of the 4G allele introduced a 1.94-fold risk of CAD compared with the 5G allele (95% confidence interval: 1.05–3.66). Determination of AGT M235T and PAI-1 genotypes before transplantation may help identify patients who are at risk for chronic renal transplant dysfunction. [ABSTRACT FROM AUTHOR]