I-allele of the angiotensin-converting enzyme insertion deletion gene polymorphism increases risk for Alzheimer’s disease in a German population

Abstract

Introduction: The Angiotensin-Converting Enzyme (ACE) Insertion Deletion (I/D) gene polymorphism (GP) has been implicated in the pathogenesis of Alzheimer's Disease. ACE degradates amyloid-beta peptide (1). Genetic variation in ACE has an effect on circulating ACE levels. In a codominant fashion homozygosity for the D-allele is associated with highest ACE plasma activity (2). Methods: We studied the ACE I/D GP and the Apolipoprotein E (ApoE) genotype in German Caucasian AD patients (n=114, 43 male, 71 female, mean age 78.9±9.5 yrs) diagnosed according to NINCDS-ADRDA criteria. Healthy individuals (n=81, 40 male, 41 female, mean age 59.7±7.4 yrs.) were included as controls in a population-based sample. Results: ACE I/D and ApoE genotypes were determined and did not interfere. ACE genotype and allele frequencies were compared between cases and controls using chi-square and Fisher exact tests. Odds ratio (OR) for AD according to ACE I/D GP was calculated using a logistic regression model. Patients and controls differed in age. AD risk was determined in a model (II vs. ID + DD) comparing II homozygotes with heterozygotes and DD homozygotes (one-tailed p=.04 OR 2.0 95% CI: .98–4.28). Conclusions: Regarding our results the ACE I/D GP should be taken into account when investigating the complex pathogenesis of AD.