Investigation of a novel role for riboflavin in blood pressure and preventing hypertension in women: Targeted randomised trials in genetically at-risk individuals

Summary

Hypertension is the leading risk factor contributing to all-cause mortality and is estimated to affect 1.13 billion people globally, resulting in over 9 million deaths annually, predominantly from cardiovascular disease (CVD). For women of reproductive age, hypertension brings an added burden, adversely affecting the health of the mother before, during and after pregnancy and of her baby in the immediate and long term. This project, which is focused on preventing hypertension in women, will investigate riboflavin as a novel, targeted approach for maintaining healthy blood pressure (BP) in women with a particular genetic risk factor affecting the way they metabolise folate, known as the MTHFR TT genotype. This genetic risk factor affects about 10% of people globally (and much higher in some regions worldwide) and is associated with higher blood pressure throughout life and a higher risk of developing hypertension.

In novel work conducted to date at the Nutrition Innovation Centre for Food and Health (NICHE), riboflavin has been shown to play an important role in controlling BP specifically in individuals affected by the TT genotype. In a study of over 6,000 Irish adults, a three-fold excess risk of hypertension was observed when this genetic risk factor occurred in combination with riboflavin deficiency, while better riboflavin status was associated with a much-reduced risk of hypertension. Moreover, in 3 previous trials in hypertensive patients, riboflavin supplementation for 16 weeks in TT individuals was shown to lower BP. No study to date has however considered the BP-lowering effect of riboflavin in healthy younger women. Furthermore, the mechanism by which riboflavin works to lower BP in genetically at risk individuals remains unclear.

Riboflavin is a much-overlooked micronutrient and deficiency may be considerably more widespread worldwide than is generally appreciated, but typically goes undetected due to lack of reliable measurements of assessment of riboflavin status. There is some evidence to suggest that poor riboflavin status appears to be a particular problem in women of childbearing years and teenage girls. Correspondingly, dietary riboflavin intakes are low in women of reproductive age globally and this could substantially exacerbate the risk of hypertension and related adverse outcomes. Supplementation with riboflavin could play a key role in reducing these risks, particularly among women affected by this genetic risk factor leading to hypertension. The aim of this PhD project, therefore, is to investigate the effectiveness of riboflavin in reducing BP in women with the MTHFR TT genotype. Furthermore, to uncover the physiological and molecular mechanisms underpinning the role of this novel gene-nutrient interaction in BP, this PhD project will also involve 1. Conducting parallel studies to measure endothelial function in response to riboflavin and 2. applying state-of-the-art genomic and epigenomic approaches to determine the biological processes linking MTHFR and riboflavin with BP.

Important Information: 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.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal
• A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Practice-based research experience and/or dissemination
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications record appropriate to career stage
• Experience of presentation of research findings

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility

This project is funded by:

• Vice Chancellor's Research Scholarship (VCRS)
• Department for the Economy (DfE)

Our fully funded PhD scholarships will cover tuition fees and provide a maintenance allowance of £19,237 (tbc) per annum for three years (subject to satisfactory academic performance).  A Research Training Support Grant (RTSG) of £900 per annum is also available.

These scholarships, funded via the Department for the Economy (DfE) and the Vice Chancellor’s Research Scholarships (VCRS), are open to applicants worldwide, regardless of residency or domicile.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies.