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Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not ^1,2,3

¹ From the Department of Nutrition, School of Public Health and School of Medicine (MDN, K-AdC, LMF, and SHZ), and the Nutrition Research Institute (SHZ), University of North Carolina at Chapel Hill, Chapel Hill, NC

Background: Some humans fed a low-choline diet develop hepatosteatosis, liver and muscle damage, and lymphocyte apoptosis. The risk of developing such organ dysfunction is increased by the presence of single-nucleotide polymorphisms (SNPs) in genes involved in folate and choline metabolism.

Objective: We investigated whether these changes that occur in the expression of many genes when humans are fed a low-choline diet differ between subjects who develop organ dysfunction and those who do not. We also investigated whether expression changes were dependent on the presence of the SNPs of interest.

Design: Thirty-three subjects aged 20–67 y were fed for 10 d a baseline diet containing the recommended adequate intake of choline. They then were fed a low-choline diet for up to 42 d or until they developed organ dysfunction. Blood was collected at the end of each phase, and peripheral lymphocytes were isolated and used for genotyping and for gene expression profiling with the use of microarray hybridization.

Results: Feeding a low-choline diet changed the expression of 259 genes, and the profiles of subjects who developed and those who did not develop signs of organ dysfunction differed. Group clustering and gene ontology analyses found that the diet-induced changes in gene expression profiles were significantly influenced by the SNPs of interest and that the gene expression phenotype of the variant gene carriers differed significantly even with the baseline diet.

Conclusion: These findings support our hypothesis that a person's susceptibility to organ dysfunction when fed a low-choline diet is modulated by specific SNPs in genes involved in folate and choline metabolism.

Key Words: Diet • choline • gene expression • lymphocytes • single-nucleotide polymorphism • methylenetetrahydrofolate dehydrogenase • MTHFD • phosphatidylethanolamine methyltransferase • PEMT • choline dehydrogenase • CHDH • choline deficiency

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