One-carbon metabolism, blood pressure and risk of hypertension through the lifecycle

Abstract

Hypertension and ineffective blood pressure (BP) control is a public health challenge of global proportions. The aim of this thesis was primarily to investigate the emerging role of one-carbon metabolism in BP and risk of hypertension through the lifecycle. As part of this work, a critical review of the literature was conducted investigating the role of nutrition, particularly one-carbon metabolism, in BP and risk of hypertension. In particular, evidence of the impact of the C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) in BP and risk of hypertension was identified. Observational findings from the Optimal Nutrition for the Prevention of Hypertension in Pregnancy (OptiPREG) study showed that the MTHFR 677TT genotype was associated with an abnormal pattern of BP change and an early elevation in BP, higher diastolic BP and potentially higher risk of hypertension in early pregnancy. Irrespective of MTHFR genotype, riboflavin deficiency was identified as an independent determinant for hypertension at the 12th gestational week. In a preliminary analysis of the ongoing OptiPREG randomised trial, intervention with riboflavin from the 18th gestational week to the end of pregnancy in women with the TT genotype prevented increases in systolic BP and serum homocysteine. In older age, results from the Trinity-Ulster and Department of Agriculture (TUDA) cohort study showed that the variant MTHFR 677TT genotype was associated with higher systolic BP up to 70 years, whilst a better riboflavin status was associated with lower BP and higher BP control rates in affected individuals. In conclusion, the findings of this thesis show that the MTHFR C677T polymorphism adversely impacts BP through the lifecycle, but riboflavin has an important modulating effect on BP in affected individuals. Hence, intervention with riboflavin could potentially provide an alternative, non-pharmacologic treatment and prevention strategy for hypertension in sub-populations globally with this genetic risk factor.

Date of Award	Jun 2020
Original language	English
Sponsors	HSC Research and Development, DSM Nutritional Products Ltd & Vice Chanchellor's Research Scholarship
Supervisor	Helene Mc Nulty (Supervisor), Kristina Pentieva (Supervisor) & Mary Ward (Supervisor)