Role of the alpha-adducin genotype on renal disease progression.
BACKGROUND
A genetic susceptibility to hypertension may predispose to the development of end-stage renal disease (ESRD) and promote a more rapid loss of renal function in patients with renal diseases. The alpha-adducin (ADD) gene, alone or in combination with the angiotensinogen (AGT) and the angiotensin-converting enzyme (ACE), is a candidate for abnormal blood pressure regulation and thus for increased susceptibility or faster progression to ESRD.


METHODS
Genotyping for the G460W-ADD, M235T-AGT and the insertion/deletion (I/D)-ACE gene polymorphisms was performed in 260 control subjects and 260 ESRD patients using polymerase chain reaction, gel analysis and appropriate restriction digest.


RESULTS
The frequencies of the ADD, AGT and ACE genotypes in ESRD patients did not differ from observed frequencies in control subjects. The average (+/-SE) time from diagnosis to the onset of ESRD tended to be shorter in the presence of the ADD-460WW (5.1 +/- 1.1 years, N = 10) than with the GW (9.9 +/- 0.7 years, N = 81) and GG (11.3 +/- 1.0 years, N = 164) genotypes (F-ratio=2.71, P = 0.068; WW vs. GW P < 0.06 and vs. GG <0.03). In the 167 patients homozygous for the ADD-G allele, a more rapid progression with the ACE-DD genotype as compared to ACE-DI and II was found (P < 0.02).


CONCLUSIONS
The ADD genotype is predictive of the course of renal function loss in an unselected renal population and influences the effect of the ACE genotype to modulate the rate of progression to ESRD. Thus, the ADD genotype may play a role for the understanding of interindividual differences in the course of renal diseases.
Nicod
Jérôme
J
Division of Nephrology and Hypertension, Inselspital, University of Berne, Berne, Switzerland.
Frey
Brigitte M
BM
Frey
Felix J
FJ
Ferrari
Paolo
P
D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011379:Prognosis; D012016:Reference Values; D013997:Time Factors; D000099291:Adducins
D000808:Angiotensinogen; D002148:Calmodulin-Binding Proteins; D007703:Peptidyl-Dipeptidase A; D000099291:Adducins