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 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12263-014-0408-4) contains supplementary material, which is available to authorized users.
Highlights
Phenotypic differences between individuals result from heterogeneous genetic makeups sharing the same environment and between genetically similar individuals exposed to different environments
Metabolite principal component 1 (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
A large number of studies have identified gene–environment interactions based on single-nucleotide polymorphisms (SNPs) and nutrient intake (Fenech et al 2011; Lee et al 2011; Ordovas et al 2011), and recent genome-wide association studies (GWAS) have identified SNPs associated with dietary preference (Hamza et al 2011; Tanaka et al 2013)
Summary
Phenotypic differences between individuals result from heterogeneous genetic makeups sharing the same environment and between genetically similar individuals exposed to different environments. A large number of studies have identified gene–environment interactions based on single-nucleotide polymorphisms (SNPs) and nutrient intake (Fenech et al 2011; Lee et al 2011; Ordovas et al 2011), and recent genome-wide association studies (GWAS) have identified SNPs associated with dietary preference (Hamza et al 2011; Tanaka et al 2013) These gene–nutrient association studies and GWAS identified individual SNPs that explain only a small fraction of the phenotype (i.e., small effect size) (Goldstein 2009). The focus on individual SNPs, copy number variations (CNVs), or other single genomic structural variations (e.g., insertion/deletions or INDELS) is based implicitly on the one gene–one enzyme hypothesis of Beadle and Tatum (Beadle and Tatum 1941) Their experimental paradigm revolutionized biomedical research by demonstrating that a mutation in a single gene could eliminate enzyme activity and produce a change in phenotype. They described biological processes more holistically in the introduction of that landmark paper:
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