Angiotensin gene polymorphism as a determinant of posttransplantation renal dysfunction and hypertension

Background. Polymorphism of the genes associated with angiotensin, includin g angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and the type 1 (AT1) and type 2 (AT2) angiotensin II receptors, has been implicated in t he pathophysiology of hypertension, ischemic heart disease, and progression of chronic renal disease. Methods. We investigated the impact of the ACE, AGT, AT1, and AT2 genotypes on renal allograft function in 148 patients (77 men, 71 women) who underwe nt transplantation over a 5-year period. Patients were genotyped using poly merase chain reaction sequence-specific primers and polymerase chain reacti on followed by restriction fragment length polymorphism. analysis. Results. ACE (D) and AGT (A/A) genotypes were associated with poorer chroni c renal transplant function and more rapid chronic progression, defined as an increase of serum creatinine level with time. In addition, mean diastoli c blood pressure at 3 years was significantly (P <0.02) correlated with C g ene dose of AT1 (A -->C, 1166), with levels of 79 +/- 10 mmHg, 82 +/-8.6 mm Hg, and 95 +/-8.3 mmHg for the A/A, A/C, and C/C genotypes, respectively. A n apparent AT2 homozygote disadvantage could be an epiphenomenon because AT 2 maps to the X chromosome, and males are homozygous for just one of the AT 2 alleles (A/- or G/-). Conclusions. Pretransplantation testing of the ACE, AGT, and AT1 genotypes may assist clinicians in identifying patients at risk for chronic renal tra nsplant dysfunction and hypertension.