Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease

Background. Previous studies concerning Alu I/D polymorphism in the ACE gen e and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual an d ethnic differences in the proportion of variance in ACE activity explaine d by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different coun tries. Methods. Blood samples were collected from 307 ADPKD patients (116 Australi an. 124 Bulgarian and 67 Polish) for determination of ACE activity levels a nd I/D genotypes. Chronic renal failure (CRF) was present in 117 patients a nd end-stage renal failure (ESRF) in 68 patients. Results. ACE activity was related to the I/D genotype, showing a dosage eff ect of the D allele (P = 0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distri bution was found between patients with CRF versus normal renal function (P = 0.494; P = 0.576) or between those with ESRF versus those without ESRF (P = 0.872. P = 0.825). No effect of the I/D genotype on age at development a nd progression to renal failure (CRF: ESRF) was detected in the overall gro up, and in subgroups based on ethnic origin, linkage status and sex. Conclusion. ACE is not likely to play a role as a determinant of ADPKD phen otype severity.