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 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.


CONCLUSIONS
ACE is not likely to play a role as a determinant of ADPKD phenotype severity.
Schiavello
T
T
Centre for Human Genetics, Edith Cowan University, Joondalup, Perth, WA, Australia.
Burke
V
V
Bogdanova
N
N
Jasik
P
P
Melsom
S
S
Boudville
N
N
Robertson
K
K
Angelicheva
D
D
Dworniczak
B
B
Lemmens
M
M
Horst
J
J
Todorov
V
V
Dimitrakov
D
D
Sulowicz
W
W
Krasniak
A
A
Stompor
T
T
Beilin
L
L
Hallmayer
J
J
Kalaydjieva
L
L
Thomas
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D002648:Child; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006973:Hypertension / Q000150:complications; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
D004251:DNA Transposable Elements; D007703:Peptidyl-Dipeptidase A