Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

M Ward; Catherine Hughes; J.J. Strain; Rosie Reilly; Conal Cunningham; Anne Molloy; Geraldine  Horigan; Miriam Casey; Kevin McCarroll; Maurice O'Kane; Michael Gibney; Albert Flynn; Janette Walton; Breige McNulty; Adrian  McCann; Laura Kirwan; John Scott; H McNulty

doi:10.1186/s12916-020-01780-x

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

M Ward
, Catherine Hughes
, J.J. Strain
, Rosie Reilly
, Conal Cunningham
, Anne Molloy
, Geraldine Horigan
, Miriam Casey
, Kevin McCarroll
, Maurice O'Kane
, Michael Gibney
, Albert Flynn
, Janette Walton
, Breige McNulty
, Adrian McCann
, Laura Kirwan
, John Scott
, H McNulty

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

257 Downloads (Pure)

Abstract

Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P

Original language	English
Article number	318
Pages (from-to)	318
Number of pages	11
Journal	BMC Medicine
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12916-020-01780-x
Publication status	Published (in print/issue) - 11 Nov 2020

Bibliographical note

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

Supported by governmental funding from the Irish Department of Agriculture, Food and the Marine and Health Research Board (under the Food Institutional Research Measure, FIRM, initiative) and from the Northern Ireland Department for Employment and Learning (under its Strengthening the All-Island Research Base initiative). The work combines two studies completed as part of an All-Ireland initiative under the Joint Irish Nutrigenomics Organisation, JINGO. The funders had no role in the study design, in the collection, analysis or interpretation of the data, in the writing of the report, or in the decision to submit for publication.

Funders
Irish Department of Agriculture, Food and the Marine and Health Research Board
Northern Ireland Department for Employment and Learning

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Blood pressure
Folate polymorphism
Hypertension
MTHFR
Personalised treatment
Prevention
Riboflavin

Access to Document

10.1186/s12916-020-01780-xLicence: CC BY

Accepted manuscriptAuthor Accepted Manuscript, 320 KBLicence: CC BY
Final published versionFinal published version, 1.44 MBLicence: CC BY

Cite this

Ward, M., Hughes, C., Strain, J. J., Reilly, R., Cunningham, C., Molloy, A., Horigan, G., Casey, M., McCarroll, K., O'Kane, M., Gibney, M., Flynn, A., Walton, J., McNulty, B., McCann, A., Kirwan, L., Scott, J., & McNulty, H. (2020). Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project. BMC Medicine, 18(1), 318. Article 318. https://doi.org/10.1186/s12916-020-01780-x

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title = "Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project",

abstract = "Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. The variant MTHFR 677TT genotype was identified in 12\% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95\% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2\% and 30.0\% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95\% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30\%) compared to those without this variant, CT (37\%) and CC (45\%) genotypes (P ",

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Ward, M , Hughes, C , Strain, JJ, Reilly, R, Cunningham, C, Molloy, A, Horigan, G, Casey, M, McCarroll, K, O'Kane, M, Gibney, M, Flynn, A, Walton, J, McNulty, B, McCann, A, Kirwan, L, Scott, J & McNulty, H 2020, 'Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project', BMC Medicine, vol. 18, no. 1, 318, pp. 318. https://doi.org/10.1186/s12916-020-01780-x

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AU - Hughes, Catherine

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AU - Reilly, Rosie

AU - Cunningham, Conal

AU - Molloy, Anne

AU - Horigan, Geraldine

AU - Casey, Miriam

AU - McCarroll, Kevin

AU - O'Kane, Maurice

AU - Gibney, Michael

AU - Flynn, Albert

AU - Walton, Janette

AU - McNulty, Breige

AU - McCann, Adrian

AU - Kirwan, Laura

AU - Scott, John

AU - McNulty, H

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AB - Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P

KW - Blood pressure

KW - Folate polymorphism

KW - Hypertension

KW - MTHFR

KW - Personalised treatment

KW - Prevention

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C2 - 33172445

SN - 1741-7015

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SP - 318

JO - BMC Medicine

JF - BMC Medicine

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ER -

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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Mary Ward

Cite this

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Profiles

Mary Ward

Cite this