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

Abstract

BACKGROUND:

Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained 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 countries.

METHODS:

Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients.

RESULTS:

ACE activity was related to the I/D genotype, showing a dosage effect 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 distribution 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 and progression to renal failure (CRF; ESRF) was detected in the overall group, 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 phenotype severity.

• Authors: T Schiavello, V Burke, N Bogdanova, P Jasik, S Melsom, N Boudville, K Robertson, D Angelicheva, B Dworniczak, M Lemmens, J Horst, V Todorov, D Dimitrakov, W Sulowicz, A Krasniak, T Stompor, L Beilin, J Hallmayer, L Kalaydjieva, M Thomas
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 16 Issue 12 Pg. 2323-7 (Dec 2001) ISSN: 0931-0509 [Print] England
• PMID: 11733623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Transposable Elements
• Peptidyl-Dipeptidase A

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Aging (physiology)
• Child
• DNA Transposable Elements
• Female
• Gene Deletion
• Humans
• Hypertension (complications)
• Kidney (physiopathology)
• Kidney Failure, Chronic (etiology)
• Male
• Middle Aged
• Peptidyl-Dipeptidase A (blood, genetics)
• Phenotype
• Polycystic Kidney, Autosomal Dominant (complications, enzymology, genetics, physiopathology)
• Polymorphism, Genetic
• Severity of Illness Index