title: Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations.
abstract: 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.CHKArs10791957,CHDHrs9001,CHDHrs12676,PEMTrs4646343,PEMTrs7946,FMO3rs2266782,SLC44A1rs7873937, andSLC44A1rs3199966 altered the use of choline as a methyl donor;CHDHrs9001 andBHMTrs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP)-choline pathway; andCHKArs10791957,CHDHrs12676,PEMTrs4646343,PEMTrs7946 andSLC44A1rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamineN-methyltransferase (PEMT) denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. abg224@cornell.edu.
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Ganz
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. vcohen20@gmail.com.
authors.forename: Vanessa V
authors.initials: VV
authors.lastname: Cohen
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. ccs229@cornell.edu.
authors.forename: Camille C
authors.initials: CC
authors.lastname: Swersky
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. jas683@cornell.edu.
authors.forename: Julie
authors.initials: J
authors.lastname: Stover
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. gav8@cornell.edu.
authors.forename: Gerardo A
authors.initials: GA
authors.lastname: Vitiello
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. lovesky.jessica@gmail.com.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lovesky
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. chuangjazz@gmail.com.
authors.forename: Jasmine C
authors.initials: JC
authors.lastname: Chuang
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. shields.kelsey@gmail.com.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Shields
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. shortforv@yahoo.com.
authors.forename: Vladislav G
authors.initials: VG
authors.lastname: Fomin
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. sanjay.mohan90@gmail.com.
authors.forename: Yusnier S
authors.initials: YS
authors.lastname: Lopez
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. anitaganti16@gmail.com.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. bradjc23@gmail.com.
authors.forename: Anita
authors.initials: A
authors.lastname: Ganti
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. ovm4@cornell.edu.
authors.forename: Bradley
authors.initials: B
authors.lastname: Carrier
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Malysheva
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA. mac379@cornell.edu.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Caudill
mesh_terms: D001622:Betaine / Q000378:metabolism; D002794:Choline / Q000097:blood / Q000378:metabolism*; D004194:Disease / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D064688:Metabolic Flux Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D064167:Recommended Dietary Allowances; D012098:Reproduction; D055815:Young Adult
chemical_list: D001622:Betaine; D002794:Choline
keywords: choline; lactation; micronutrient metabolism; nutrigenetics; nutritional genomics; one-carbon metabolism; pregnancy; single nucleotide polymorphisms