Methylation potential associated with diet, genotype, protein, and metabolite levels in the Delta Obesity Vitamin Study

Authors: MONTEIRO, JACQUELINE - Universidad De Sao Paulo; WISE, CAROLYN - Food And Drug Administration(FDA); MORINE, MELISSA - University Of Trento, Italy; TEITEL, CANDEE - Food And Drug Administration(FDA); PENCE, LISA - Food And Drug Administration(FDA); WILLIAMS, ANNA - 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; NING, BAITANG - Food And Drug Administration(FDA); OGUNTIMEIN, JOAN - Drexel University; TAYLOR, LAUREN - Emory University; TOENNESSEN, TERRI - Food And Drug Administration(FDA); PRIAMI, CORRADO - University Of Trento, Italy; BEGER, RICHARD - Food And Drug Administration(FDA); BOGLE, MARGARET - Retired ARS Employee; KAPUT, JIM - Food And Drug Administration(FDA)

Submitted to: Genes and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/6/2014
Publication Date: 4/30/2014
Citation: Monteiro, J.P., Wise, C., Morine, M.J., Teitel, C., Pence, L., Williams, A., Mccabe-Seller, B., Champagne, C., Turner, J., Shelby, B., Ning, B., Oguntimein, J., Taylor, L., Toennessen, T., Priami, C., Beger, R., Bogle, M., Kaput, J. 2014. Methylation potential associated with diet, genotype, protein, and metabolite levels in the Delta Obesity Vitamin Study. Genes and Nutrition. 9:403.

Interpretive Summary: In a group of 45 children attending a summer day camp over 2 years, a number of variables were measured: 24-hour food intake, eight vitamins, over 1,100 blood proteins, and three one-carbon metabolites. Advanced statistical analysis identified two groups of children based on the levels of the one-carbon metabolites in blood which reflected vitamin status – those with relatively normal values and those deficient in several B vitamins. This approach identified 46 normal genetic variants in 25 genes that enable researchers to identify those who may have different nutrient requirements.

Technical Abstract: Micronutrient research typically focuses on analyzing the effects of single or a few nutrients on health by analyzing a limited number of biomarkers. The observational study described here analyzed micronutrients, plasma proteins, dietary intakes, and genotype using a systems approach. Participants attended a community-based summer day program for 6–14 year old in 2 years. Genetic makeup, blood metabolite and protein levels, and dietary differences were measured in each individual. Twenty-four-hour dietary intakes, eight micronutrients (vitamins A, D, E, thiamin, folic acid, riboflavin, pyridoxal, and pyridoxine) and 3 one-carbon metabolites [homocysteine (Hcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)], and 1,129 plasma proteins were analyzed as a function of diet at metabolite level, plasma protein level, age, and sex. Cluster analysis identified two groups differing in SAM/SAH and differing in dietary intake patterns indicating that SAM/SAH was a potential marker of nutritional status. The approach used to analyze genetic association with the SAM/SAH metabolites is called middle-out: SNPs in 275 genes involved in the one-carbon pathway (folate, pyridoxal/pyridoxine, thiamin) or were correlated with SAM/SAH (vitamin A, E, Hcy) were analyzed instead of the entire 1M SNP data set. This procedure identified 46 SNPs in 25 genes associated with SAM/SAH demonstrating a genetic contribution to the methylation potential. Individual plasma metabolites correlated with 99 plasma proteins. Fourteen proteins correlated with body mass index, 49 with group age, and 30 with sex. The analytical strategy described here identified subgroups for targeted nutritional interventions.