ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes

TY - JOUR

T1 - ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes

AU - Færch, Louise H

AU - Sejling, Anne-Sophie

AU - Lajer, Maria

AU - Tarnow, Lise

AU - Thorsteinsson, Birger

AU - Pedersen-Bjergaard, Ulrik

N1 - © The Author(s) 2013.

PY - 2015/6/15

Y1 - 2015/6/15

N2 - Aims: 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 Hillerd 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) 1.016)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.01.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not. Conclusion: 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.

AB - Aims: 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 Hillerd 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) 1.016)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.01.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not. Conclusion: 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.

KW - Adult

KW - Cohort Studies

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - INDEL Mutation

KW - Male

KW - Peptidyl-Dipeptidase A

KW - Phenotype

KW - Proportional Hazards Models

KW - Renin-Angiotensin System

U2 - 10.1177/1470320313494431

DO - 10.1177/1470320313494431

M3 - Journal article

C2 - 23833037

SN - 1470-3203

VL - 16

SP - 374

EP - 381

JO - Journal of the Renin-Angiotensin-Aldosterone System

JF - Journal of the Renin-Angiotensin-Aldosterone System

IS - 2

ER -