The 677C~ T polymorphism in the gene encoding the folate-metabolising enzyme MTHFR is associated with an increased risk of several disease outcomes, including cardiovascular disease (CVD). Although this polymorphism has recently been linked with higher blood pressure (BP), no previous study has investigated its role as a determinant of hypertension throughout adulthood. Riboflavin acts as a cofactor for MTHFR and previous work at this Centre has shown that intervention with riboflavin results in significant BP-Iowering specifically in patients with the homozygous mutant MTHFR 677TT genotype, but whether this gene-nutrient interaction is an important determinant of hypertension is not known. Furthermore, although this polymorphism is also linked with neural tube defects (NTDs), the potential implications for folate recommendations to prevent NTDs in women who carry this genetic risk factor have not previously been considered. The aims of this thesis therefore were to investigate the role of this polymorphism, and any relevant gene-nutrient interactions, as a determinant of BP, and to consider folate requirements for preventing NTDs specifically in this genetically at-risk group. Analysis of data from two large observational studies of Irish adults (n 5225) demonstrated, for the first time, that adults with the MTHFR 677TT genotype from aged 18yrs onwards have a significantly increased risk of developing hypertension, but this risk can be substantially reduced through optimising riboflavin (and to a lesser extent, folate) status. Preliminary results from a randomised trial provide no evidence to support a BP-Iowering effect of folic acid in adults with the TT genotype, but provide some further evidence that age influences the BP phenotype and the potential to reduce BP through targeted intervention in these individuals. Analysis of data from a pregnancy cohort investigated in this thesis highlights the particular importance for women with the TT genotype to strictly adhere to the recommendation of commencing folic acid prior to conception (as recommended) for NTD prevention. In conclusion, this thesis demonstrates a role for the MTHFR 677C T polymorphism as a determinant of hypertension and highlights the important role of optimal B-vitamin status in modulating disease risk in adults with this genetic variant. These findings have important public health implications.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:673806 |
| Date | January 2013 |
| Creators | Reilly, Rose |
| Publisher | Ulster University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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