Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

被引：44

作者：

Ganz, Ariel B. ^{[1
]}

Cohen, Vanessa V. ^{[1
]}

Swersky, Camille C. ^{[1
]}

Stover, Julie ^{[1
]}

Vitiello, Gerardo A. ^{[1
]}

Lovesky, Jessica ^{[1
]}

Chuang, Jasmine C. ^{[1
]}

Shields, Kelsey ^{[1
]}

Fomin, Vladislav G. ^{[1
]}

Lopez, Yusnier S. ^{[1
]}

Mohan, Sanjay ^{[1
]}

Ganti, Anita ^{[1
]}

Carrier, Bradley ^{[1
]}

Malysheva, Olga V. ^{[1
]}

Caudill, Marie A. ^{[1
]}

机构：

[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2017年 / 18卷 / 02期

基金：

美国食品与农业研究所; 美国国家卫生研究院;

关键词：

choline; nutritional genomics; nutrigenetics; single nucleotide polymorphisms; pregnancy; lactation; one-carbon metabolism; micronutrient metabolism; HOMOCYSTEINE METHYLTRANSFERASE BHMT; PHOSPHOLIPID-METABOLISM; DIETARY REQUIREMENT; MONOOXYGENASE; FATTY LIVER; PHOSPHATIDYLETHANOLAMINE; POLYMORPHISMS; PHOSPHATIDYLCHOLINE; NUTRIENT; PATHWAY;

D O I：

10.3390/ijms18020252

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Single nucleotide polymorphisms (SNPs) in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75) consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9) for 10-12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP)-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT) denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

引用

页数：23

共 46 条

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