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Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort

Silver, MJ; Corbin, KD; Hellenthal, G; da Costa, K-A; Dominguez-Salas, P; Moore, SE; Owen, J; ... Zeisel, SH; + view all (2015) Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort. The FASEB Journal , 29 (8) pp. 3426-3435. 10.1096/fj.15-271056. Green open access

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Abstract

Choline is an essential nutrient, and the amount needed in the diet is modulated by several factors. Given geographical differences in dietary choline intake and disparate frequencies of single-nucleotide polymorphisms (SNPs) in choline metabolism genes between ethnic groups, we tested the hypothesis that 3 SNPs that increase dependence on dietary choline would be under negative selection pressure in settings where choline intake is low: choline dehydrogenase (CHDH) rs12676, methylenetetrahydrofolate reductase 1 (MTHFD1) rs2236225, and phosphatidylethanolamine-N-methyltransferase (PEMT) rs12325817. Evidence of negative selection was assessed in 2 populations: one in The Gambia, West Africa, where there is historic evidence of a choline-poor diet, and the other in the United States, with a comparatively choline-rich diet. We used 2 independent methods, and confirmation of our hypothesis was sought via a comparison with SNP data from the Maasai, an East African population with a genetic background similar to that of Gambians but with a traditional diet that is higher in choline. Our results show that frequencies of SNPs known to increase dependence on dietary choline are significantly reduced in the low-choline setting of The Gambia. Our findings suggest that adequate intake levels of choline may have to be reevaluated in different ethnic groups and highlight a possible approach for identifying novel functional SNPs under the influence of dietary selective pressure.

Type: Article
Title: Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort
Open access status: An open access version is available from UCL Discovery
DOI: 10.1096/fj.15-271056
Publisher version: http://dx.doi.org/ 10.1096/fj.15-271056
Language: English
Additional information: Copyright © The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: diet and selection, adequate intake levels, phosphatidylethanolamine-N-methyltransferase, choline dehydrogenase, methylenetetrahydrofolate dehydrogenase
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/1481397
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