Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T polymorphisms: Risk of chronic renal failure

Background. Chronic renal failure (CRF) is a complex phenotype that results from an underlying kidney disease and superimposing environmental and gene tic factors. The aim of our study was to evaluate the role of polymorphisms in the genes encoding for components of the renin-angiotensin system (RAS) in the development and/or progression of CRF. Methods. Two hundred forty-seven family trios (patients with CRF and both p arents; 120 with primary chronic glomerulonephritis, 80 with interstitial n ephritis, and 47 with type 1 diabetes with nephropathy) were examined, and transmission/ disequilibrium test (TDT) was used to evaluate allele transmi ssion from heterozygous parents to affected offspring. Results. The D allele of the angiotensin I-converting enzyme (ACE) gene ins ertion/deletion polymorphism was transmitted significantly more frequently than expected for no association among all examined trios and in the subgro up of patients with interstitial nephritis. The angiotensinogen 235T allele was transmitted significantly more frequently to patients with CRF than ex pected for no association, but the effect was seen only in patients with in terstitial nephritis. The presence of the DD or ID genotype was associated with a faster rate of decline of renal function, which was not observed for the angiotensinogen M235T polymorphism. For chymase gene and angiotensin I I receptor type 1 gene, allele transmission did not deviate significantly f rom a random proportion of 50:50%. Conclusions. The results of this study suggest that ACE gene insertion/dele tion and angiotensinogen M235T polymorphisms contribute to the increased ri sk for the development of CRF, but the magnitude of the effect within subse ts of patients with specific etiologies of CRF must be evaluated further.