University of Oulu

Karjalainen, J., Mononen, N., Hutri-Kähönen, N. et al. The effect of apolipoprotein E polymorphism on serum metabolome – a population-based 10-year follow-up study. Sci Rep 9, 458 (2019).

The effect of apolipoprotein E polymorphism on serum metabolome : a population-based 10-year follow-up study

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Author: Karjalainen, Juho-Pekka1; Mononen, Nina1; Hutri-Kähönen, Nina2;
Organizations: 1Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
2Department of Pediatrics, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
3Department of Medicine, University of Turku, and Division of Medicine, Turku University Hospital, Turku, Finland, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
4Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
5NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
6Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
7Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
8Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
9Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, VIC, Australia
10Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
11Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.7 MB)
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Language: English
Published: Springer Nature, 2019
Publish Date: 2020-02-14


Apolipoprotein E (apoE) is the key regulator of plasma lipids, mediating altered functionalities in lipoprotein metabolism — affecting the risk of coronary artery (CAD) and Alzheimer’s diseases, as well as longevity. Searching pathways influenced by apoE prior to adverse manifestations, we utilized a metabolome dataset of 228 nuclear-magnetic-resonance-measured serum parameters with a 10-year follow-up from the population-based Young Finns Study cohort of 2,234 apoE-genotyped (rs7412, rs429358) adults, aged 24–39 at baseline. At the end of our follow-up, by limiting FDR-corrected p < 0.05, regression analyses revealed 180/228 apoE-polymorphism-related associations with the studied metabolites, in all subjects — without indications of apoE x sex interactions. Across all measured apoE- and apoB-containing lipoproteins, ε4 allele had consistently atherogenic and ε2 protective effect on particle concentrations of free/esterified cholesterol, triglycerides, phospholipids and total lipids. As novel findings, ε4 associated with glycoprotein acetyls, LDL-diameter and isoleucine — all reported biomarkers of CAD-risk, inflammation, diabetes and total mortality. ApoE-subgroup differences persisted through our 10-year follow-up, although some variation of individual metabolite levels was noticed. In conclusion, apoE polymorphism associate with a complex metabolic change, including aberrations in multiple novel biomarkers related to elevated cardiometabolic and all-cause mortality risk, extending our understanding about the role of apoE in health and disease.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 9
Article number: 458
DOI: 10.1038/s41598-018-36450-9
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This study was financially supported by the Juhani Aho Foundation for Medical Research (and the formerly known Research Foundation of Clinical Chemistry), the Päivikki and Sakari Sohlberg Foundation, and the Faculty of Medicine and Life Sciences, University of Tampere. The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; Finnish Cultural Foundation, Pirkanmaa Regional fund; Tampereen Yliopistollisen sairaalan tukisäätiö, and EU Horizon 2020 (grant 755320 for TAXINOMISIS); and European Research Council (grant 742927 for MULTIEPIGEN project). The quantitative serum NMR metabolomics platform and its development have been supported by the Academy of Finland, TEKES (the Finnish Funding Agency for Technology and Innovation), the Sigrid Juselius Foundation, the Novo Nordisk Foundation, the Finnish Diabetes Research Foundation, the Paavo Nurmi Foundation, and strategic and infrastructural research funding from the University of Oulu, Finland, as well as by the British Heart Foundation, the Wellcome Trust and the Medical Research Council, UK. The expert data management by Irina Lisinen is gratefully acknowledged. M.A.-K. works in a Unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1).
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