University of Oulu

Ville Rantalainen, Jari Lahti, Eero Kajantie, Pentti Tienari, Johan G. Eriksson, Katri Raikkonen, APOE ɛ4, rs405509, and rs440446 promoter and intron-1 polymorphisms and dementia risk in a cohort of elderly Finns—Helsinki Birth Cohort Study, Neurobiology of Aging, Volume 73, 2019, Pages 230.e5-230.e8, ISSN 0197-4580, https://doi.org/10.1016/j.neurobiolaging.2018.09.005

APOE ɛ4, rs405509, and rs440446 promoter and intron-1 polymorphisms and dementia risk in a cohort of elderly Finns : Helsinki Birth Cohort Study

Saved in:
Author: Rantalainen, Ville1; Lahti, Jari1; Kajantie, Eero2;
Organizations: 1Department of Psychology and Logopedics, University of Helsinki, Finland; Folkhälsan Research Centre, Helsinki, Finland
2Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Hospital for Children and Adolescents, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland; PEDEGO Research Unit, MRC Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
3Department of Neurology, Helsinki University Central Hospital; Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland
4Department of General Practice, Primary Health Care, University of Helsinki, Helsinki University Hospital, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland
5Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019060618863
Language: English
Published: Elsevier, 2019
Publish Date: 2019-09-12
Description:

Abstract

We tested if the ε4 major isoform of the APOE gene and rs405509 and rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or Alzheimer’s disease with diagnoses derived from the Hospital Discharge and Causes of Death Registers in 1453 participants of the Helsinki Birth Cohort Study. We used Cox proportional hazard models adjusted for sex, year of birth, maximum lifetime occupational status and education, and diagnoses of stroke, coronary heart disease, mood disorders, and depressive symptoms. APOE ε4 predicted higher risk of any dementia (hazard ratios >3.68; 95% confidence interval [CI] 1.76, 7.70) across all statistical models, and when adjusted for rs405509 and rs440446. The number of minor alleles in rs405509 or rs440446 was not associated with dementia risk (hazard ratios <1.43; 95% CI 0.87, 2.36). As rs405509 or rs440446 has been associated with nonpathological cognitive aging in this and other cohorts independent of the APOE major isoforms, these findings lend credence that APOE locus may be linked with dementia risk and nonpathological cognitive aging via separate mechanisms.

see all

Series: Neurobiology of aging
ISSN: 0197-4580
ISSN-E: 1558-1497
ISSN-L: 0197-4580
Volume: 73
Pages: 230.e5 - 230.e8
DOI: 10.1016/j.neurobiolaging.2018.09.005
OADOI: https://oadoi.org/10.1016/j.neurobiolaging.2018.09.005
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3124 Neurology and psychiatry
Subjects:
Funding: The Helsinki Birth Cohort Study has been funded by The Academy of Finland (grant numbers 269925, 311617, 127437, 129306, 130326, 134791, and 263924), the Finnish Diabetes Research society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Signe and Ane Gyllenberg Foundation, Sigrid Juselius Foundation, Foundation for Pediatric Research, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation, Juho Vainio Foundation, Foundation for Cardiovascular Research, Helsinki University Hospital, and the European Commission within the 7th Framework Programme (DORIAN, grant agreement no. 278603), European Union Horizon 2020 programme (DYNAHEALTH grant no. 633595) and European Union Horizon 2020 programme (LifeCycle grant no. 733206) and European Union Horizon 2020 programme RECAP Research on Children and Adults Born Preterm grant no. 733280).
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/