Influence of ACE (I/D) and G460W polymorphism of alpha-adducin in autosomal dominant polycystic kidney disease.
BACKGROUND
The deleterious effect of the DD genotype of ACE in autosomal dominant polycystic kidney disease (ADPKD) remains controversial. Small sample size, population admixture and lack of consideration of parameters modulating the effects of ACE genotype, such as gender or alpha-adducin (ADD) genotype, might explain the discrepancy.


METHODS
We investigated the effect of ACE (I/D) polymorphism on the age at end-stage renal disease (ESRD) in a homogeneous population of 191 ADPKD patients, according to gender and genotype for the G460W polymorphism of ADD. Cumulative renal survival was assessed in 276 patients from the same families.


RESULTS
Though no effect was detected in the whole population, analysis of the male subset (n = 97) showed that patients harbouring the DD genotype of ACE had a 5-year lower mean age at ESRD than DI + II patients [47.8 +/- 1.8 (n = 31) vs 52.8 +/- 1.1 (n = 66), respectively] (P = 0.02). Furthermore, cumulative renal survival was lower in the corresponding pedigrees [47 +/- 1 years, 95% confidence interval (CI) 45-49, vs 51 +/- 1 years, 95% CI 48-54]. The G460W polymorphism of ADD had no effect on the age at ESRD and cumulative renal survival, either alone or in combination with the ACE (I/D) polymorphism.


CONCLUSIONS
In this large series of ADPKD patients, we found no effect of the ACE (I/D) polymorphism on the age at ESRD, either alone or in combination with the G460W polymorphism of ADD. However, a deleterious effect of the DD genotype of ACE on renal disease progression was observed in ADPKD males.
D017677:Age Distribution; D017668:Age of Onset; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D019062:Cell Adhesion Molecules, Neuron-Glia / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D017678:Sex Distribution; D016019:Survival Analysis; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D019062:Cell Adhesion Molecules, Neuron-Glia; D007703:Peptidyl-Dipeptidase A; D000099291:Adducins