Blood Pressure and Central Haemodynamics in Healthy Adults Stratified by MTHFR Genotype (RAFA Obs)

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

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.

Study Overview

• Status: Completed
• Conditions: Blood Pressure

• Study Type: Observational
• Enrollment (Actual): 498

Contacts and Locations

Study Locations

• United Kingdom
  • Co.Londonderry
    • Coleraine, Co.Londonderry, United Kingdom, BT52 1SA
      • Human Intervention Studies Unit, Ulster University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Community sample

Description

Inclusion Criteria:

• Pre-screened for MTHFR 677TT genotype
• Aged at least 18 years old

Exclusion Criteria:

• Younger than 18 years
• Pregnant

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
TT MTHFR genotype
Non-TT (i.e. CC/CT) MTHFR genotype

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Ulster

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2011
• Primary Completion (Actual): August 15, 2019
• Study Completion (Actual): August 15, 2019

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 30, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Blood Pressure; Folic Acid; MTHFR; Methylenetetrahydrofolate Reductase; Riboflavin; Central Hemodynamics; Folate Polymorphism
• Other Study ID Numbers: REC/11/0081 Obs

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No