The effect of apolipoprotein E polymorphism on serum metabolome : a population-based 10-year follow-up study
Karjalainen, Juho-Pekka; Mononen, Nina; Hutri-Kähönen, Nina; Lehtimäki, Miikael; Juonala, Markus; Ala-Korpela, Mika; Kähönen, Mika; Raitakari, Olli; Lehtimäki, Terho (2019-01-24)
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). https://doi.org/10.1038/s41598-018-36450-9
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https://urn.fi/URN:NBN:fi-fe202002145499
Tiivistelmä
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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