Interaction Between Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism and Angiotensin-Converting Enzyme Inhibition on Survival in Hemodialyzed Patients

Abstract

The association between ACE (angiotensin-converting enzyme) gene insertion/deletion (I/D) polymorphism and mortality has been inconsistently observed in earlier studies in patients on maintenance hemodialysis. We hypothesized that the effect of ACE gene I/D polymorphism on mortality may be influenced by concurrent ACE inhibitor therapy in this population.

In this prospective, multicenter cohort, observational study, data was collected from 716 prevalent chronic hemodialysis patients, blood samples were genotyped for I/D single nucleotide polymorphism. Patient mortality was assessed in tree genotype groups insertion/insertion, insertion/deletion and deletion/deletion (I/I, I/D, and D/D) using multivariate Cox proportional hazard models.

The most frequent genotype was I/D (42.6%), followed by D/D (37.7%) and I/I (19.7%) genotypes. The mean age was 54.9 ± 15.5 years, 53.2% of all patients were male and in the total group the prevalence of diabetes was 19.3%. ACE inhibitor therapy was prescribed for 47.9% of all patients. The median duration of dialysis before blood sampling was 23.8 months (IQR 11.2–47.1). Patients were followed for 10 years, the median follow-up time was 29.8 months (IQR 12.6–63.4). Patient characteristics were well balanced among the genotype groups. D/D genotype, was associated with inferior survival (I/I vs D/D: log-rank test: P = 0.04) in patients not receiving ACE inhibitor therapy, and the presence of this therapy diminished this difference. There was no difference in survival among unselected patients with different genotypes. In multivariate Cox regression models, D/D genotype (compared to I/I) was a significant predictor of mortality only in patients without ACE inhibitor therapy (HR 0.67, 95% CI 0.46–0.97, P = 0.03).

Our data suggests that hemodialyzed patients with the deletion/deletion (D/D) genotype might have inferior outcome, and ACE inhibitor therapy may be associated with improved survival in this subgroup.