title: Choline metabolites: gene by diet interactions.
abstract: OBJECTIVE
  The review highlights recent advances in our understanding of the interactions between genetic polymorphisms in genes that metabolize choline and the dietary requirements of choline and how these interactions relate to human health and disease.
  
  
  RESULTS
  The importance of choline as an essential nutrient has been well established, but our appreciation of the interaction between our underlying genetic architecture and dietary choline requirements is only beginning. It has been shown in both human and animal studies that choline deficiencies contribute to diseases such as nonalcoholic fatty liver disease and various neurodegenerative diseases. An adequate supply of dietary choline is important for optimum development, highlighted by the increased maternal requirements during fetal development and in breast-fed infants. We discuss recent studies investigating variants in PEMT and MTHFR1 that are associated with a variety of birth defects. In addition to genetic interactions, we discuss several recent studies that uncover changes in fetal global methylation patterns in response to maternal dietary choline intake that result in changes in gene expression in the offspring. In contrast to the developmental role of adequate choline, there is now an appreciation of the role choline has in cardiovascular disease through the gut microbiota-mediated metabolite trimethylamine N-oxide. This pathway highlights some of our understanding of how the microbiome affects nutrient processing and bioavailability. Finally, to better characterize the genetic architecture regulating choline requirements, we discuss recent results focused on identifying polymorphisms that regulate choline and its derivative products.
  
  
  CONCLUSIONS
  Here we discuss recent studies that have advanced our understanding of how specific alleles in key choline metabolism genes are related to dietary choline requirements and human disease.
authors.affiliation: aDepartment of Genetics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina bDepartment of Preventive Medicine and Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California cNutrition Research Institute, University of North Carolina Kannapolis, Kannapolis dDepartment of Nutrition, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Tangi
authors.initials: T
authors.lastname: Smallwood
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bennett
mesh_terms: D000818:Animals; D002794:Choline / Q000378:metabolism*; D006801:Humans; D008744:Methylamines / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism
chemical_list: D008744:Methylamines; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C494489:PEMT protein, human; D050918:Phosphatidylethanolamine N-Methyltransferase; C005855:trimethyloxamine; D002794:Choline