Cargando…

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

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 u...

Descripción completa

Detalles Bibliográficos
Autores principales: Ganz, Ariel B., Cohen, Vanessa V., Swersky, Camille C., Stover, Julie, Vitiello, Gerardo A., Lovesky, Jessica, Chuang, Jasmine C., Shields, Kelsey, Fomin, Vladislav G., Lopez, Yusnier S., Mohan, Sanjay, Ganti, Anita, Carrier, Bradley, Malysheva, Olga V., Caudill, Marie A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343788/
https://www.ncbi.nlm.nih.gov/pubmed/28134761
http://dx.doi.org/10.3390/ijms18020252
_version_ 1782513423991439360
author Ganz, Ariel B.
Cohen, Vanessa V.
Swersky, Camille C.
Stover, Julie
Vitiello, Gerardo A.
Lovesky, Jessica
Chuang, Jasmine C.
Shields, Kelsey
Fomin, Vladislav G.
Lopez, Yusnier S.
Mohan, Sanjay
Ganti, Anita
Carrier, Bradley
Malysheva, Olga V.
Caudill, Marie A.
author_facet Ganz, Ariel B.
Cohen, Vanessa V.
Swersky, Camille C.
Stover, Julie
Vitiello, Gerardo A.
Lovesky, Jessica
Chuang, Jasmine C.
Shields, Kelsey
Fomin, Vladislav G.
Lopez, Yusnier S.
Mohan, Sanjay
Ganti, Anita
Carrier, Bradley
Malysheva, Olga V.
Caudill, Marie A.
author_sort Ganz, Ariel B.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5343788
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-53437882017-03-16 Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations Ganz, Ariel B. Cohen, Vanessa V. Swersky, Camille C. Stover, Julie Vitiello, Gerardo A. Lovesky, Jessica Chuang, Jasmine C. Shields, Kelsey Fomin, Vladislav G. Lopez, Yusnier S. Mohan, Sanjay Ganti, Anita Carrier, Bradley Malysheva, Olga V. Caudill, Marie A. Int J Mol Sci Article 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. MDPI 2017-01-26 /pmc/articles/PMC5343788/ /pubmed/28134761 http://dx.doi.org/10.3390/ijms18020252 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ganz, Ariel B.
Cohen, Vanessa V.
Swersky, Camille C.
Stover, Julie
Vitiello, Gerardo A.
Lovesky, Jessica
Chuang, Jasmine C.
Shields, Kelsey
Fomin, Vladislav G.
Lopez, Yusnier S.
Mohan, Sanjay
Ganti, Anita
Carrier, Bradley
Malysheva, Olga V.
Caudill, Marie A.
Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations
title Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations
title_full Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations
title_fullStr Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations
title_full_unstemmed Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations
title_short Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations
title_sort genetic variation in choline-metabolizing enzymes alters choline metabolism in young women consuming choline intakes meeting current recommendations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343788/
https://www.ncbi.nlm.nih.gov/pubmed/28134761
http://dx.doi.org/10.3390/ijms18020252
work_keys_str_mv AT ganzarielb geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT cohenvanessav geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT swerskycamillec geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT stoverjulie geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT vitiellogerardoa geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT loveskyjessica geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT chuangjasminec geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT shieldskelsey geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT fominvladislavg geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT lopezyusniers geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT mohansanjay geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT gantianita geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT carrierbradley geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT malyshevaolgav geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations
AT caudillmariea geneticvariationincholinemetabolizingenzymesalterscholinemetabolisminyoungwomenconsumingcholineintakesmeetingcurrentrecommendations