Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not.
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.


METHODS
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.


CONCLUSIONS
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.
Niculescu
Mihai D
MD
Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461, USA.
da Costa
Kerry-Ann
KA
Fischer
Leslie M
LM
Zeisel
Steven H
SH
D000328:Adult; D000368:Aged; D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D050545:Choline Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D016000:Cluster Analysis; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000096:biosynthesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
D004247:DNA; D050545:Choline Dehydrogenase; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline