title: ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes.
abstract: OBJECTIVE
  Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all-cause mortality in three single-institution outpatient cohorts.
  
  
  METHODS
  Genotype-based analyses were performed in 269 patients from Hillerød Hospital (HIH) (follow-up: 12 years) and in 439 patients with diabetic nephropathy and 437 patients with persistent normoalbuminuria from the Steno Diabetes Center (SDC) (follow-up: 9.5 years). Patients not on renin-angiotensin system (RAS)-blocking treatment were included in analyses of serum ACE activity (HIH: n = 208) and plasma ACE concentration (SDC: n=269).
  
  
  RESULTS
  In the HIH cohort, carrying a D-allele was associated with excess mortality (hazard ratio (HR) = 4.0 (95% confidence interval (CI) 1.0-16)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.0-1.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not.
  
  
  CONCLUSIONS
  In unselected patients with type 1 diabetes, carrying the ACE D-allele and high spontaneous serum ACE activity were associated with 12-year excess mortality. These findings could not be reproduced in two other cohorts with persistent normoalbuminuria or diabetic nephropathy.
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, Denmark Louise.Faerch@regionh.dk.
authors.forename: Louise H
authors.initials: LH
authors.lastname: Færch
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, Denmark.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Sejling
authors.affiliation: Steno Diabetes Center, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Lajer
authors.affiliation: Steno Diabetes Center, Denmark Health, University of Aarhus, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, Denmark Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Birger
authors.initials: B
authors.lastname: Thorsteinsson
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Pedersen-Bjergaard
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D016016:Proportional Hazards Models; D012084:Renin-Angiotensin System / Q000235:genetics
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: ACE ID polymorphism; ACE activity; T1DM; diabetic nephropathy; mortality; normoalbuminuria