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

• Published in: BMC medicine Vol. 18; no. 1; p. 318
• Main Authors: Ward, Mary, Hughes, Catherine F, Strain, J J, Reilly, Rosie, Cunningham, Conal, Molloy, Anne M, Horigan, Geraldine, Casey, Miriam, McCarroll, Kevin, O'Kane, Maurice, Gibney, Michael J, Flynn, Albert, Walton, Janette, McNulty, Breige A, McCann, Adrian, Kirwan, Laura, Scott, John M, McNulty, Helene
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.11.2020; BioMed Central; BMC
• Subjects: Adults; Age; Aged; Antihypertensive Agents - therapeutic use; Antihypertensives; Biomarkers; Blood pressure; Blood Pressure - genetics; Care and treatment; Cholesterol; Cohort Studies; Confidence intervals; Enzymes; Female; Folate polymorphism; Gene polymorphism; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Genomes; Genotype & phenotype; Genotypes; Health aspects; Health risk assessment; Homocysteine; Human nutrition; Humans; Hypertension; Hypertension - drug therapy; Hypertension - genetics; Hypertension - metabolism; Laboratories; Lifestyles; Male; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; MTHFR; Nutrigenomics; Nutrition; Older people; Personalised treatment; Polymorphism; Polymorphism, Single Nucleotide; Reductases; Riboflavin; Riboflavin - metabolism; Risk; Risk Factors; Statistical analysis; Variables; Variance analysis; Vitamin B; United Kingdom; United Kingdom > UK; Ireland; Hypertension; Prevention; Riboflavin; Folate polymorphism; MTHFR; Blood pressure; Personalised treatment
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-020-01780-x

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 < 0.027). The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.