The effect of apolipoprotein E polymorphism on serum metabolome - a population-based 10-year follow-up study
: Karjalainen J-P., Mononen N., Hutri-Kähönen N., Lehtimäki M., Juonala M., Ala-Korpela M., Kähönen M., Raitakari O., Lehtimäki T.
Publisher: NATURE PUBLISHING GROUP
: 2019
: Scientific Reports
: SCIENTIFIC REPORTS
: SCI REP-UK
: ARTN 458
: 9
: 14
: 2045-2322
DOI: https://doi.org/10.1038/s41598-018-36450-9
: https://www.nature.com/articles/s41598-018-36450-9
: https://research.utu.fi/converis/portal/detail/Publication/39425132
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.
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