Genetic associations with micronutrient levels identified in immune and gastrointestinal networks

Authors: MORINE, MELISSA - University Of Trento, Italy; MONTEIRO, JACQUELINE - Universidad De Sao Paulo; WISE, CAROLYN - Food And Drug Administration(FDA); TEITEL, CANDEE - Food And Drug Administration(FDA); PENCE, LISA - Food And Drug Administration(FDA); WILLIAMS, ANNA - Food And Drug Administration(FDA); NING, BAITANG - Food And Drug Administration(FDA); MCCABE-SELLER, BEVERLY - Retired ARS Employee; CHAMPAGNE, CATHERINE - Pennington Biomedical Research Center; TURNER, JEROME - Boys, Girls, Adults Community Development Center, Inc; SHELBY, BEATRICE - Boys, Girls, Adults Community Development Center, Inc; BOGLE, MARGARET - Retired ARS Employee; BEGER, RICHARD - Food And Drug Administration(FDA); PRIAMI, CORRADO - University Of Trento, Italy; KAPUT, JIM - Food And Drug Administration(FDA)

Submitted to: Genes and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/2014
Publication Date: 5/28/2014
Citation: Morine, M.J., Monteiro, J.P., Wise, C., Teitel, C., Pence, L., Williams, A., Ning, B., Mccabe-Seller, B., Champagne, C., Turner, J., Shelby, B., Bogle, M., Beger, R.D., Priami, C., Kaput, J. 2014. Genetic associations with micronutrient levels identified in immune and gastrointestinal networks. Genes and Nutrition. 9:408.

Interpretive Summary: Children aged 6-14 years attending a summer day camp had blood samples drawn and were assessed for a range of vitamins and plasma proteins over two years. In addition, they were asked about their food intake and genetic makeup was evaluated. A pattern of metabolites was identified that indicated low vitamin B status and a specific pattern of proteins in blood interacting with genetic involvement of immune and gastrointestinal functions. This pilot study of 45 children suggests individuality in response to diet but must be confirmed in a much larger study.

Technical Abstract: The discovery of vitamins and clarification of their role in preventing frank essential nutrient deficiencies occurred in the early 1900s. Much vitamin research has understandably focused on public health and the effects of single nutrients to alleviate acute conditions. The physiological processes for maintaining health, however, are complex systems that depend upon interactions between multiple nutrients, environmental factors, and genetic makeup. To analyze the relationship between these factors and nutritional health, data were obtained from an observational, community-based participatory research program of children and teens (age 6–14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin, and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and nutrient status was assessed with 24-h dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythrocyte SAM/SAH, Hcy, and 5 vitamins were identified by principal component analysis. Met_PC1 levels were significantly associated with (1) single-nucleotide polymorphisms, (2) levels of plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and immune functions, as identified in a global network of metabolic/protein–protein interactions. Subsequent mining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships thatmining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships that may be explained by gene–nutrient interactions. The systems nutrition strategy described here has thus associated a multivariate metabolite pattern in blood with genes involved in immune and gastrointestinal functions.