The ACE Gene Is Associated with Late-Life Major Depression and Age at Dementia Onset in a Population-Based Cohort

Am J Geriatr Psychiatry. 2017 Feb;25(2):170-177. doi: 10.1016/j.jagp.2016.06.009. Epub 2016 Jun 23.

Abstract

Objective: Depression and dementia in the elderly have been suggested to share similar risk factors and pathogenetic background, and recently the authors reported that the APOEɛ4 allele is a risk factor for both disorders in the general population. The aim of the present study was to examine the influence of the well-known polymorphisms rs1799752 in the angiotensin-converting enzyme (ACE) and rs5186 in the angiotensin receptor II type 1 (AGTR1) on late-life depression and dementia in a population-based Swedish cohort of older individuals followed over 12 years.

Methods: In 2000-2001, 900 individuals underwent neuropsychiatric and neuropsychological examinations. Follow-up evaluations were performed in 2005-2006 and 2009-2010, and register data on dementia to 2012 were included. Cross-sectional associations between genotypes/alleles and depression and dementia at baseline and between genotypes/alleles and depression on at least one occasion during the study period and dementia onset to 2012 were investigated.

Results: As previously found for rs1799752 in ACE, rs5186 in AGTR1 was associated with dementia at baseline (OR: 3.25 [CI: 1.42-7.06], z = 2.90, p = 0.004). These associations became substantially weaker, or disappeared, when dementia onset to 2012 was included. For rs1799752 this could be explained by a significant association with age at onset (mean: 79.5 [SD: 6.45] years for risk-genotype carriers and 81.7 [SD: 7.12] years for carriers of other genotypes, b = -2.43, t = -2.38, df = 192, p = 0.02). When individuals with major depression on at least one occasion were analyzed, a significant association (OR: 2.14 [95% CI: 1.13-4.20], z = 2.28, p = 0.02), remaining after exclusion of dementia, with rs1799752 in ACE was found.

Conclusion: In this population-based sample of older individuals, genetic variations in ACE seem to be important both for late-life major depression and dementia.

Keywords: Late-life depression; angiotensin receptor II type 1; angiotensin-converting enzyme; dementia; gene.

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Cross-Sectional Studies
  • Dementia / genetics*
  • Depressive Disorder, Major / genetics*
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Logistic Models
  • Male
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic
  • Prospective Studies
  • Receptor, Angiotensin, Type 1 / genetics
  • Sweden

Substances

  • AGTR1 protein, human
  • Receptor, Angiotensin, Type 1
  • ACE protein, human
  • Peptidyl-Dipeptidase A