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Sci Rep. 2019 Jan 24;9(1):458. doi: 10.1038/s41598-018-36450-9.

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

Author information

1
Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. juhopekka.karjalainen@gmail.com.
2
Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
3
Department of Pediatrics, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
4
Department of Medicine, University of Turku, and Division of Medicine, Turku University Hospital, Turku, Finland, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
5
Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
6
NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
7
Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
8
Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
9
Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
10
Department 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.
11
Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
12
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Abstract

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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