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Thus, we used stable isotope liquid chromatography\u2010mass spectrometry (LC\u2010MS) methodology to examine the impact of candidate SNPs on choline metabolism in a long\u2010term, randomized, controlled feeding trial among pregnant, lactating, and nonpregnant (NP) women consuming 480 or 930 mg\/d choline (22% as choline\u2010d\n                    <jats:sub>9<\/jats:sub>\n                    , with d\n                    <jats:sub>9<\/jats:sub>\n                    indicating a deuterated trimethyl amine group) and meeting folate\u2010intake recommendations. Variants impairing folate metabolism, methylenetetrahydrofolate reductase (\n                    <jats:italic>MTHFR<\/jats:italic>\n                    ) rs1801133, methionine synthase (\n                    <jats:italic>MTR<\/jats:italic>\n                    ) rs1805087 [wild\u2010type (WT)],\n                    <jats:italic>MTR<\/jats:italic>\n                    reductase (\n                    <jats:italic>MTR<\/jats:italic>\n                    R) rs1801394, and methylenetetrahydrofolate dehydrogenase\u2010methenyltetrahydrofolate cyclohydrolase\u2010formyltetrahydrofolate synthetase (\n                    <jats:italic>MTHFD1<\/jats:italic>\n                    ) rs2236225, influenced choline dynamics, frequently through interactions with reproductive state and choline intake, with fewer genotypic alterations observed among pregnant women. Women with these variants partitioned more dietary choline toward phosphatidylcholine (PC) biosynthesis\n                    <jats:italic>via<\/jats:italic>\n                    the cytidine diphosphate (CDP)\u2010choline pathway at the expense of betaine synthesis even when use of betaine as a methyl donor was increased. Choline intakes of 930 mg\/d restored partitioning of dietary choline between betaine and CDP\u2010PC among NP (MTHFR rs1801133 and\n                    <jats:italic>MTR<\/jats:italic>\n                    rs1805087 WT) and lactating (\n                    <jats:italic>MTHFD1<\/jats:italic>\n                    rs2236225) women with risk genotypes. Overall, our findings indicate that loss\u2010of\u2010function variants in folatemetabolizing enzymes strain cellular PC production, possibly\n                    <jats:italic>via<\/jats:italic>\n                    impaired folate\u2010dependent phosphatidylethanolamine\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyltransferase (PEMT)\u2010PC synthesis, and suggest that women with these risk genotypes may benefit from choline intakes exceeding current recommendations.\u2014Ganz, A. B., Shields, K., Fomin, V. G., Lopez, Y. S., Mohan, S., Lovesky, J., Chuang, J.C., Ganti, A., Carrier, B., Yan, J., Taeswuan, S., Cohen, V.V., Swersky, C. C., Stover, J.A., Vitiello, G.A., Malysheva, O. V., Mudrak, E., Caudill, M. A. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis. FASEB J. 30, 3321\u20133333 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201500138rr","type":"journal-article","created":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T21:58:37Z","timestamp":1466805517000},"page":"3321-3333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis"],"prefix":"10.1096","volume":"30","author":[{"given":"Ariel B.","family":"Ganz","sequence":"first","affiliation":[{"name":"Division of Nutritional Sciences Cornell University  Ithaca New York 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