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

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• 作者：Anna Zettergren ; Ph.D.^a ; ^{anna.zettergren@neuro.gu.se} ; Silke Kern ; M.D. ; Ph.D.^a ; ^c ; Deborah Gustafson ; Ph.D.^a ; Pia Gudmundsson ; Ph.D.^a ; Robert Sigströ ; m ; M.D. ; Ph.D.^a ; Svante Ö ; stling ; M.D. ; Ph.D.^a ; Elias Eriksson ; M.D. ; Ph.D.^b ; Henrik Zetterberg ; M.D. ; Ph.D.^c ; ^d ; Kaj Blennow ; M.D. ; Ph.D.^c ; Ingmar Skoog ; M.D. ; Ph.D.^a
• 关键词：Late-life depression ; dementia ; gene ; angiotensin-converting enzyme ; angiotensin receptor II type 1
• 刊名：The American Journal of Geriatric Psychiatry
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：25
• 期：2
• 页码：170-177
• 全文大小：169 K
• 卷排序：25

文摘

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