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Title: Genetic associations with micronutrient levels identified in immune and gastrointestinal networks

Author
item MORINE, MELISSA - Universidad De Sao Paulo
item MONTEIRO, JACQUELINE - University Of Trento, Italy
item WISE, CAROLYN - Delta Nutrition Intervention Research Iniative (NIRI)
item TEITEL, CANDEE - Delta Nutrition Intervention Research Iniative (NIRI)
item PENCE, LISA - Delta Nutrition Intervention Research Iniative (NIRI)
item WILLIAMS, ANNA - Delta Nutrition Intervention Research Iniative (NIRI)
item NING, BAITANG - Delta Nutrition Intervention Research Iniative (NIRI)
item MCCABE-SELLERS, BEVERLY - Delta Nutrition Intervention Research Iniative (NIRI)
item CHAMPAGNE, CATHERINE - Pennington Biomedical Research Center
item TURNER, JEROME - Delta Nutrition Intervention Research Iniative (NIRI)
item SHELBY, BEATRICE - Delta Nutrition Intervention Research Iniative (NIRI)
item BOGLE, MARGARET - Delta Nutrition Intervention Research Iniative (NIRI)
item BEGER, RICHARD - Delta Nutrition Intervention Research Iniative (NIRI)
item PRIAMI, CORRADO - University Of Trento, Italy
item KAPUT, JAMES - Nestle

Submitted to: Genes and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/2014
Publication Date: 5/31/2014
Citation: Morine, M.J., Monteiro, J.P., Wise, C., Teitel, C., Pence, L., Williams, A., Ning, B., Mccabe-Sellers, 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 DOI 10.1007/s12263-014-0408-4.

Interpretive Summary: Biological processes that result in health or disease are inherently complex, but many research studies try to reduce that complexity to a single process or measurement of a single vitamin. Researchers analyzed micronutrient levels and other metabolites in blood samples of children who attended the Boys, Girls, Adults Development Center's summer day camp in Marvel, AR, and used a systems analysis approach to evaluate their observations. This strategy uses computer-based methods to identify novel associations between what an individual eats, or their blood levels of vitamins or proteins, with their genetic makeup. More importantly, this systems approach analyzes the blood level responses of individuals to their dietary intake patterns. This method identified genes involved in gastrointestinal and immune functions that contribute to vitamin levels in the blood and at the same time showed that diet also influenced these vitamin levels. This research provides the foundation for similar studies being conducted in populations throughout the world and aids in developing strategies for targeted nutritional interventions.

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 was obtained from an observational, community-based participatory research (CBPR) program of children and teens (ages 6 to 14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-denosylmethionine [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 conducted at 3 time points in each of two years. Genetic make-up was analyzed with 1M SNP genotyping arrays, and nutrient status was assessed with 24-hr dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythrocyte SAM:SAH, Hcy, and 6 vitamins were identified by principal component analysis. Met_PC1 levels correlated with (i) SNPs, (ii) levels of plasma proteins, and (iii) multi-locus 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 that may be explained by gene - nutrient interactions. The systems nutrition strategy described here has thus associated a complex metabolite pattern in blood with genes associated with immune and gastrointestinal functions.