The ACE Insertion Deletion polymorphism relates to dementia by metabolic phenotype, APOEe{open}4, and age of dementia onset

The renin-angiotensin system (RAS) may play a role in dementia pathogenesis because of its effects on vascular and metabolic homeostasis, amyloid metabolism, and learning and memory. The angiotensin-converting enzyme (ACE), a pivotal RAS protein, is encoded for by a gene containing a functional ID variant, which has been related to dementia risk. We examined the relationship between the ACE Insertion Deletion (ACE ID) variant and dementia with consideration for metabolic phenotypes, age and APOEe{open}4 using a population-based, cross-sectional sample of 891 Swedish women and men aged 70-92 years, of whom 61 people were demented. The odds of dementia was two-fold higher among those with ACE II genotype, and ranged from 2.18 to 4.35 among those with dementia onset ≤70 years, an APOEe{open}4 allele, systolic blood pressure <160mmHg, body mass index <25kg/m², and in women only, waist circumference ≤88cm and hip circumference <101cm. Variations among reports on the relationship between the ACE ID polymorphism and dementia may be due to lack of consideration for gene-gene and gene-phenotype associations.