A1 Refereed original research article in a scientific journal

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




AuthorsKarjalainen J-P., Mononen N., Hutri-Kähönen N., Lehtimäki M., Juonala M., Ala-Korpela M., Kähönen M., Raitakari O., Lehtimäki T.

PublisherNATURE PUBLISHING GROUP

Publication year2019

JournalScientific Reports

Journal name in sourceSCIENTIFIC REPORTS

Journal acronymSCI REP-UK

Article numberARTN 458

Volume9

Number of pages14

ISSN2045-2322

DOIhttps://doi.org/10.1038/s41598-018-36450-9

Web address https://www.nature.com/articles/s41598-018-36450-9

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/39425132


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, e4 allele had consistently atherogenic and epsilon 2 protective effect on particle concentrations of free/esterified cholesterol, triglycerides, phospholipids and total lipids. As novel findings, epsilon 4 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.

Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.





Last updated on 2024-26-11 at 12:49