Common genetic polymorphisms affect the human requirement for the nutrient choline - PubMed (original) (raw)

Comparative Study

Common genetic polymorphisms affect the human requirement for the nutrient choline

Kerry-Ann da Costa et al. FASEB J. 2006 Jul.

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.

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Figures

Figure 1

Figure 1

Three important genes in choline metabolism for which we identified single nucleotide polymorphisms. PEMT = phosphatidylethanolamine N-methyltransferase, which catalyzes the reaction to make phosphatidylcholine (PtdCho) from phosphatidylethanolamine (PtdEtn) using S-adenosylmethionine (SAM) to donate methyl groups; CHDH = choline dehydrogenase, which along with betaine aldehyde dehydrogenase irreversibly oxidizes choline (Cho) to form betaine (Bet); BHMT = betaine:homocysteine methyltransferase, which donates its methyl group to homocysteine (Hcy) to form methionine (Met); PCho = phosphocholine.

Figure 2

Figure 2

Study design. Healthy men and women were fed a baseline diet containing the choline Adequate Intake concentration for 10 days. They were then switched to a low choline diet (<50 mg choline) until they developed signs of organ dysfunction associated with choline deficiency or for up to 42 days. Subjects who developed signs of organ dysfunction were repleted with graded amounts of choline at 10 day intervals until their symptoms disappeared; those without signs of organ dysfunction were fed the 100% choline diet for at least 3 days before being discharged from the study. Some subjects were given a folic acid supplement (400 μg per day) during the depletion and repletion phases, but this did not affect their susceptibility to choline deficiency (from da Costa et al., Am J. Clinc. Nutr., in press).

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