Approximately 12% of the world's population have a have a common C677T polymorphism in the gene encoding the folate metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the polymorphism (TT genotype) causes an increased requirement for the B-vitamins folic acid and riboflavin and more importantly results in an increased risk of developing high blood pressure (BP). Previous work from our Centre has demonstrated significantly higher BP in those with the TT genotype. This work has been conducted in cohorts with premature cardiovascular disease (CVD) and hypertension without overt CVD, but the effect in younger, healthier individuals is unexplored. To date our studies have also focused on BP as the primary outcome, but newer markers of vascular health including central pressure and hemodynamics have emerged as superior prognostic indicators of CVD. The effect of the TT genotype on these measures is an area for investigation and may help us understand the mechanism linking the genotype with BP, which is currently unknown. As adults with the TT genotype have increased requirements for riboflavin and folic acid, and BP in TT adults appears to be riboflavin dependent, the influence of these vitamins on central measures is an area for consideration. Study Design This is an observational study investigating the blood pressure profiles of healthy adults aged 18-65 years, stratified by MTHFR genotype. Apparently healthy adults will be recruited from workplaces and the general community across Northern Ireland and screened for the polymorphism via buccal swab. Those with the TT genotype and a similar number of non-TT (i.e. CC/CT) genotype individuals will be contacted and asked to come to a one-off appointment. Brachial BP will be assessed by an electronic BP monitor, central BP and central haemodynamics (augmentation index, augmentation pressure and pulse wave velocity) will be assessed by SphygmoCor XCEL. In addition, anthropometric measurements, health and lifestyle infromation and a blood sample will be obtained. Data will be statistically analysed using SPSS software to if determine differences between gentoype groups exist.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
2,564
1.6 mg riboflavin / day for 24 weeks
0.4 mg folic acid / day for 24 weeks
Human Intervention Studies Unit, Ulster University
Coleraine, Co.Londonderry, United Kingdom
Blood pressure
Office blood pressure
Time frame: Change from baseline to 24 weeks
Central blood pressure
Measured using SphygmoCor device
Time frame: Change from baseline to 24 weeks
Pulse wave analysis
Measured using SphygmoCor device
Time frame: Change from baseline to 24 weeks
Pulse wave velocity
Measured using SphygmoCor device
Time frame: Change from baseline to 24 weeks
Red blood cell riboflavin
Measured using erythrocyte glutathione reductase activity coefficient (EGRAC)
Time frame: Change from baseline to 24 weeks
Red blood cell folate
Measured by microbiological assay
Time frame: Change from baseline to 24 weeks
Serum homocysteine
Measured using an immunoassay
Time frame: Change from baseline to 24 weeks
Plasma vitamin B6
Measured by High Performance Liquid Chromatography
Time frame: Change from baseline to 24 weeks
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