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Common genetic polymorphisms affect the human requirement for the nutrient choline
Author(s) -
Costa Kerry-Ann,
Kozyreva Olga G.,
Song Jiannan,
Galanko Joseph A.,
Fischer Leslie M.,
Zeisel Steven H.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-5734com
Subject(s) - choline , single nucleotide polymorphism , biology , snp , homocysteine , allele , genetics , methylenetetrahydrofolate reductase , endocrinology , gene , genotype
ABSTRACT 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 A→C;rs9001) had a protective effect on susceptibility to choline deficiency, while a second CHDH variant (+432 G→T;rs12676) was associated with increased susceptibility to choline deficiency. A SNP in the PEMT coding region (+ 5465 G→A; rs7946) and a betaine:homocysteine methyltransferase (BHMT) SNP (+742 G→A; 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. FASEB J. 20, 1336–1344 (2006)