APOE and dementia - resequencing and genotyping in 105,597 individuals.

Autor:	Rasmussen KL; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.; Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark., Tybjaerg-Hansen A; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.; Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark.; Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Nordestgaard BG; Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark.; Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev, Denmark., Frikke-Schmidt R; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.; Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2020 Dec; Vol. 16 (12), pp. 1624-1637. Date of Electronic Publication: 2020 Aug 18.
DOI:	10.1002/alz.12165
Abstrakt:	Introduction: The mechanism behind the strong association between the ɛ2/ɛ3/ɛ4 apolipoprotein E gene (APOE) polymorphism and Alzheimer's disease is not well-characterized. Because low plasma levels of apoE associate with risk of dementia, genetic variants altering apoE levels in general may also associate with dementia. Methods: The APOE gene was sequenced in 10,369 individuals, and nine amino acid-changing variants with frequencies ≥2/10,000 were further genotyped in 95,228 individuals. Plasma apoE levels were measured directly. Results: Risk of all dementia and Alzheimer's disease (AD) increased with decreasing genetically determined apoE levels (P = 5 × 10 -4 and P = 1 × 10 -4 after APOE ɛ2/ɛ3/ɛ4 adjustment). Hazard ratios (95% confidence intervals) for all dementia and AD were 2.76 (1.39 to 5.47) and 4.92 (2.36 to 10.29) for the group with the genetically lowest apoE versus ɛ33. Discussion: We found that genetically low apoE levels increase and genetically high levels decrease risk, beyond ɛ2/ɛ3/ɛ4. This underscores that dementia risk more likely relates to variants affecting levels of apoE. (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu