Blood Pressure and Central Haemodynamics in Healthy Adults Stratified by MTHFR Genotype

Study Overview
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Brief Summary
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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) appears to result in 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 thus an important 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 appear to 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 attend 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 information and a blood sample will be obtained. Data will be statistically analysed using SPSS software to if determine differences between gentoype groups exist.

Official Title
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Blood Pressure Lowering Effect of B-vitamins in Adults With a Genetic Pre-disposition to Elevated Blood Pressure.

Conditions
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Blood Pressure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-screened for MTHFR 677TT genotype Aged at least 18 years old Exclusion Criteria: Younger than 18 years Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TT MTHFR genotype<br> | |
| Non-TT (i.e. CC/CT) MTHFR genotype<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Office blood pressure | One day, one measurement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial blood pressure | Measured using SphygmoCor device | One day, one measurement | 
| Central blood pressure | Measured using SphygmoCor device | One day, one measurement | 
| Pulse wave analysis | Measured using SphygmoCor device | One day, one measurement | 
| Pulse wave velocity | Measured using SphygmoCor device | One day, one measurement | 
| Riboflavin status | Measured by by EGRac | One day, one measurement | 
| Folate status | Measured by microbiological assay | One day, one measurement | 
| PLP status | Measured by HPLC | One day, one measurement | 
| Homocysteine status | Measured by GCMS | One day, one measurement | 
| One-carbon metabolite status | Measured by GCMS-MS | One day, one measurement | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Riboflavin, Blood Pressure, MTHFR, Methylenetetrahydrofolate Reductase, Central Hemodynamics, Folic Acid, Folate Polymorphism