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FASEB J. 2015 Aug;29(8):3426-35. doi: 10.1096/fj.15-271056. Epub 2015 Apr 28.

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

Author information

1
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
2
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom steven_zeisel@unc.edu.

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.

KEYWORDS:

adequate intake levels; choline dehydrogenase; diet and selection; methylenetetrahydrofolate dehydrogenase; phosphatidylethanolamine-N-methyltransferase

PMID:
25921832
PMCID:
PMC4511208
DOI:
10.1096/fj.15-271056
[Indexed for MEDLINE]
Free PMC Article

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