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  Dr Diane Lees-Murdock, Prof Mary Ward  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Hypertension, currently affecting 1 in 7 people in N. Ireland, is a major risk factor for cardiovascular disease, and in particular stroke. This project will investigate an epigenetic signature for hypertension and the effect of genotype and related B vitamins on this signature. The 677TT genotype in MTHFR, carried by 10% of people in Northern Ireland, has been identified as a risk factor for hypertension. MTHFR, which is involved in one carbon metabolism, supplies methyl groups for regulation of gene expression by DNA methylation. Riboflavin is a co-factor for the MTHFR enzyme and this gene-nutrient interaction has been shown to play an important role in hypertension. Nutrients involved in one carbon metabolism such as riboflavin, therefore have the potential to influence DNA methylation. We have previously shown that intervention with riboflavin lowers blood pressure specifically in people with the TT genotype, independent of concurrent antihypertensive therapy. This project will investigate the epigenetic modifying effect of riboflavin to find new modifiable targets for hypertension treatment.

Please note: Applications for more than one PhD studentship are welcome, however if you apply for more than one PhD project within Biomedical Sciences, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.


Recommended reading:
1. Global BPgeu Consortium. Genome-wide association study of blood pressure and hypertension. Nat Gen. 2009, 41, 666
2. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase Nat Genet. 1995, 10, 111
3. Amenyah SD, Hughes CF, Ward M, Rosborough S, Deane J, Thursby SJ, Walsh CP, Kok DE, Strain JJ, McNulty H, Lees-Murdock DJ. Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis. Nutr Rev. 2020 Aug 1;78(8):647-666
4. Amenyah SD, Ward M, Strain JJ, McNulty H, Hughes CF, Dollin C, Walsh CP, Lees-Murdock DJ. Nutritional Epigenomics and Age-Related Disease. Curr Dev Nutr. 2020 Jun 6;4(7):nzaa097
5.Horigan G, McNulty H, Ward M, Strain JJ, Purvis J, Scott JM. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C-->T polymorphism in MTHFR. J. Hypertens. 2010, 28, 478
6. Wilson CP, Ward M, McNulty H, Strain JJ, Trouton TG, Horigan G, Purvis J, Scott JM. Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: A 4-y follow-up. Am J Clin Nutr. 2012, 95:766–72.
7. Wilson CP, McNulty H, Ward M, Strain JJ, Trouton TG, Hoeft BA, Weber P, Roos FF, Horigan G, McAnena L, et al. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: Findings of a targeted randomized trial. Hypertension. 2013, 61:1302–8.
8. Ward et al. Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project. BMC Med. 2020, 11;18(1):318.
9. Amenyah SD, McMahon A, Ward M, Deane J, McNulty H, Hughes CF, Strain JJ, Horigan G, Purvis J, Walsh CP, Lees-Murdock DJ Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype. 2020, Biochimie 173, 17-26.
10. Amenyah SD, Ward M, McMahon A, Deane J, McNulty H, Hughes CF, Strain JJ, Horigan G, Purvis J, Walsh CP, Lees-Murdock DJ DNA methylation of hypertension-related genes and effect of riboflavin supplementation in adults stratified by genotype for the MTHFR C677T polymorphism 2021, International Journal of Cardiology 322, 233-239.
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