Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T polymorphisms: risk of chronic renal failure. End-Stage Renal Disease Study Group.

BACKGROUND

Chronic renal failure (CRF) is a complex phenotype that results from an underlying kidney disease and superimposing environmental and genetic 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 parents; 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with type 1 diabetes with nephropathy) were examined, and transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring.

RESULTS

The D allele of the angiotensin I-converting enzyme (ACE) gene insertion/deletion polymorphism was transmitted significantly more frequently than expected for no association among all examined trios and in the subgroup of patients with interstitial nephritis. The angiotensinogen 235T allele was transmitted significantly more frequently to patients with CRF than expected for no association, but the effect was seen only in patients with interstitial 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 II receptor type 1 gene, allele transmission did not deviate significantly from a random proportion of 50:50%.

CONCLUSIONS

The results of this study suggest that ACE gene insertion/deletion and angiotensinogen M235T polymorphisms contribute to the increased risk for the development of CRF, but the magnitude of the effect within subsets of patients with specific etiologies of CRF must be evaluated further.