APOE ε4, rs405509, and rs440446 promoter and intron-1 polymorphisms and dementia risk in a cohort of elderly Finns-Helsinki Birth Cohort Study

NEUROBIOLOGY OF AGING

卷:73

Article

Rantalainen, Ville^1,2  Lahti, Jari^1,2  Kajantie, Eero^3,4,5  Tienari, Pentti^6,7  Eriksson, Johan G.^2,8,9  Raikkonen, Katri¹ 

[1] Univ Helsinki, Dept Psychol & Logoped, Helsinki, Finland

[2] Folkhalsan Res Ctr, Helsinki, Finland

[3] Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland

[4] Univ Helsinki, Helsinki Univ Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland

[5] Univ Oulu, Oulu Univ Hosp, PEDEGO Res Unit, MRC Oulu, Oulu, Finland

[6] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland

[7] Univ Helsinki, Mol Neurol, Res Programs Unit, Biomedicum, Helsinki, Finland

[8] Univ Helsinki, Helsinki Univ Hosp, Dept Gen Practice, Primary Hlth Care, Helsinki, Finland

[9] Natl Inst Hlth & Welf, Helsinki, Finland

关键词: Dementia;    Alzheimer's disease;    APOE;    Cohort studies;   

DOI  :  10.1016/j.neurobiolaging.2018.09.005

来源: Elsevier

【 摘 要 】

We tested if the epsilon 4 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 epsilon 4 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. (C) 2018 Elsevier Inc. All rights reserved.

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