A genetic epidemiological study in British adults and older adults shows a high heritability of the combined indicator of vitamin B12 status (cB12) and connects B12 status with utilization of mitochondrial substrates and energy metabolism

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Title: A genetic epidemiological study in British adults and older adults shows a high heritability of the combined indicator of vitamin B12 status (cB12) and connects B12 status with utilization of mitochondrial substrates and energy metabolism
Authors: Dalmia, A
Dib, M-J
Maude, H
Harrington, DJ
Sobczyńska-Malefora, A
Andrew, T
Ahmadi, KR
Item Type: Journal Article
Abstract: Vitamin B12 deficiency is common among older adults. However, the most commonly used marker of deficiency, total serum vitamin B12 (B12), is not sensitive enough to diagnose true deficiency in a significant proportion of the population. The combined indicator of B12 status (cB12), formulated as a composite score of various biomarkers of vitamin B12 status (which also accounts for low folate status and age) has been shown to offer a more robust and powerful test to diagnose B12 deficiency. There are no epidemiological studies of cB12 variability in older adults. We carried out a twin study to characterize the relative contribution of heritable (h2) and environmental factors to the observed variability in cB12 score in an adult and older adult population (n=378). Furthermore, we tested for association between variability in cB12 and candidate polymorphisms and genes previously associated with B12 biomarker levels characterized in silico the mechanism linking the genetic variants and cB12 variability. We found the variability in cB12 and its constituents to be highly heritable (h2=55%–64%). The single nucleotide polymorphism rs291466 in HIBCH, previously associated with variation in MMA, was significantly associated with cB12 (R2=5%, P=5E-04). Furthermore, variants in MTRR, MMAB and MUT, underlying inborn errors of B12 metabolism, were nominally associated with variation in cB12. Pathway accompanied by expression quantitative trait loci analysis revealed that HIBCH rs291466 influences the concentration of MMA via the valine degradation pathway. Our study provides etiological insight into how B12 deficiency can manifest into impaired mitochondrial function through perturbations in mitochondrial “fuel” usage.
Issue Date: 1-Aug-2019
Date of Acceptance: 25-Apr-2019
URI: http://hdl.handle.net/10044/1/70937
DOI: https://doi.org/10.1016/j.jnutbio.2019.04.008
ISSN: 0955-2863
Publisher: Elsevier
Start Page: 156
End Page: 163
Journal / Book Title: The Journal of Nutritional Biochemistry
Volume: 70
Copyright Statement: © 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: G0901017
Keywords: Nutrition & Dietetics
0601 Biochemistry and Cell Biology
0908 Food Sciences
1111 Nutrition and Dietetics
Publication Status: Published
Embargo Date: 2020-05-14
Open Access location: https://reader.elsevier.com/reader/sd/pii/S0955286318310325?token=C69F2CBA8DAC1B303C6BCFFF985B2DA507C246D5EA58EB1FBC24FB5A5EDB67F86D7FD467937EC00B55FC92CA0F4D61D9
Online Publication Date: 2019-05-14
Appears in Collections:Department of Medicine



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