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Background The C677T polymorphism in the gene‐encoding methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk of hypertension and cardiovascular disease. Riboflavin, the MTHFR cofactor, is an important modulator of blood pressure (BP) in adults homozygous for this polymorphism (TT genotype). The effect of this genetic variant on BP and related central haemodynamic parameters in healthy adults has not been previously investigated and was examined in this study. Methods Brachial BP, central BP and pulse wave velocity (PWV, SphygmoCor XCEL) were measured in adults aged 18–65 years prescreened for MTHFR genotype. Riboflavin status was assessed using the erythrocyte glutathione reductase activation coefficient assay. Results Two hundred and forty‐two adults with the MTHFR 677TT genotype and age‐matched non‐TT (CC/CT) genotype controls were identified from a total cohort of 2546 adults prescreened for MTHFR genotype. The TT genotype was found to be an independent determinant of hypertension (p = 0.010), along with low‐riboflavin status (p = 0.002). Brachial systolic and diastolic BP were higher in TT versus non‐TT adults by 5.5 ± 1.2 and 2.4 ± 0.9 mmHg, respectively (both p < 0.001). A stronger phenotype was observed in women, with an almost 10 mmHg difference in mean systolic BP in TT versus non‐TT genotype groups: 134.9 (95% confidence interval [CI] 132.1–137.6) versus 125.2 (95% CI 122.3–128.0) mmHg; p < 0.001. In addition, PWV was faster in women with the TT genotype (p = 0.043). Conclusion This study provides the first evidence that brachial and central BP are significantly higher in adults with the variant MTHFR 677TT genotype and that the BP phenotype is more pronounced in women.

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