N05035: Application of proteome technologies to the determination of elements of the expressed genome responsive to folate intake

Study Duration: September 2001 to September 2003

Contractor: University of Sheffield

Diet imposes on the genotype to render certain population groups at greater risk for disease. Low dose folate supplementation in healthy subjects lowered plasma total homocysteine (tHcy), a biomarker of vascular risk, but did not improve a physiological measure of vascular function. In contrast, pharmacological intakes of folate in patients with coronary artery disease (CAD) lowered plasma tHcy and improved vascular dysfunction.

It is hypothesised that low dose, Hcy-lowering, folate supplementation to healthy individuals is associated with a change in the expressed proteome reflective of improved vascular health. This hypothesis will be tested using blood samples stored from a recent low-dose folate intervention study (N05002/N05006) of healthy individuals as well as blood samples collected from a high-dose folate intervention study of patients with CAD. Powerful proteomic technologies will be used to evaluate the effects of dietary folate (low and high dose) and the modulating effects of methylene tetrahydrofolate reductase (MTHFR) genotype (C677T), on protein expression polymorphisms and post-synthetic modification by oxidation. This information will inform debate concerning individual variation in micronutrient requirements.

The study will be carried out using samples collected and stored from N05006/N05006, which tested the efficacy of low-dose folate supplementation on tHcy-lowering in healthy subjects and those collected and stored from a study of high-dose folate supplementation in patients with coronary artery disease.

This project will apply proteomic methodologies to stored plasma samples from both these studies to characterise the effect of dietary folate and methylene tetrahydrofolate (MTHFR) genotype on protein expression polymorphisms and post-synthetic protein oxidation. Recent advances in proteomics and genomics allow us to undertake comparative analysis of the phenotype of individuals with the purpose of identifying a fingerprint of dietary micronutrient sensitivity, which may be reflected in an altered pattern of protein expression. Proteomics allows the assessment of both genetic and environmental factors important to the development of diseases with multifactorial aetiology. The project offers an exciting novel approach to exploring variation in micronutrient requirements. Understanding genotype/phenotype interactions is crucial to setting dietary recommendations in a manner which takes into account the heterogeneity of the UK population.

Blood samples were collected from coronary artery disease (CAD) patients before and after a period of high dose folate supplements and from healthy subjects after a period of low dose folate supplements.

Proteins were extracted from these samples and subjected to detailed analysis. We found no measureable effect of folate on the pattern of proteins in the plasma of either group of subjects, neither did we find evidence that folate reduced the amount of damaged plasma proteins.

Conclusions
The study demonstrated the complexity of the pattern of proteins seen in human plasma and indicated that more sensitive techniques might be required to detect small changes in the concentration of proteins present in low amounts. We do not rule out the possibility that folate had effects on the pattern of proteins in vascular tissue itself, that might influence vascular health.

Final report is available from the FSA Library and Information centre.
To obtain a copy, please contact the Enquiry Desk, Dr Elsie Widdowson Library and Information Services, Food Standards Agency ( Tel: 020 7276 8181/8182 ) or e-mail infocentre@foodstandards.gsi.gov.uk).

Contact: For any enquiries concerning this research project, please contact the relevant Programme contact or email science@foodstandards.gsi.gov.uk