ANGIOTENSINOGEN AND PLASMINOGEN ACTIVATOR INHIBITOR‐1 GENE POLYMORPHISM IN RELATION TO CHRONIC ALLOGRAFT DYSFUNCTION

Abstract

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.