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* Department of Nutrition, School of Public Health and School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;
Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; and
Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
1Correspondence: Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, CB# 7461, Chapel Hill, NC 27599, USA. E-mail: steven_zeisel{at}unc.edu
Humans eating diets deficient in the essential nutrient choline can develop organ dysfunction. We hypothesized that common single nucleotide polymorphisms (SNPs) in genes involved in choline metabolism influence the dietary requirement of this nutrient. Fifty-seven humans were fed a low choline diet until they developed organ dysfunction or for up to 42 days. We tested DNA SNPs for allelic association with susceptibility to developing organ dysfunction associated with choline deficiency. We identified an SNP in the promoter region of the phosphatidylethanolamine N-methyltransferase gene (PEMT; –744 G
C; rs12325817) for which 18 of 23 carriers of the C allele (78%) developed organ dysfunction when fed a low choline diet (odds ratio 25, P=0.002). The first of two SNPs in the coding region of the choline dehydrogenase gene (CHDH; +318 AC; rs9001) had a protective effect on susceptibility to choline deficiency, while a second CHDH variant (+432 GT; rs12676) was associated with increased susceptibility to choline deficiency. A SNP in the PEMT coding region (+5465 GA; rs7946) and a betaine:homocysteine methyltransferase (BHMT) SNP (+742 GA; rs3733890) were not associated with susceptibility to choline deficiency. Identification of common polymorphisms that affect dietary requirements for choline could enable us to identify individuals for whom we need to assure adequate dietary choline intake.—da Costa, K.-A., Kozyreva, O. G., Song, J., Galanko, J. A., Fischer, L. M., Zeisel, S. H. Common genetic polymorphisms affect the human requirement for the nutrient choline.
Key Words: choline deficiency • phosphatidylethanolamine N-methyltransferase • PEMT • choline dehydrogenase • CHDH • betaine:homocysteine methyltransferase • BHMT • genetic polymorphism
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