Abstract
Hypertension remains a public health burden despite advances in its management. Hence, the search for further risk stratification tools and prevention and new treatment approaches continues. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with hypertension. Interestingly, riboflavin, as a cofactor of MTHFR, may control blood pressure in patients with mutant MTHFR variants. These double benefits of a risk stratification tool and treatment approach make it interesting. Because this polymorphism depends on ethnicity and geographic region, we aimed to determine the association between MTHFR C677T gene polymorphism and hypertension in a rural Indonesian-Sundanese population. This population-based case-control study included 213 hypertensive subjects and 202 nonhypertensive subjects as controls. The TaqMan assay was used to determine the MTHFR C677T genotypes. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the risk of association. There was a significant difference in MTHFR C677T allele frequencies between the hypertensive and control groups (62.9% CC, 34.3% CT, 2.8% TT vs. 77.7% CC, 20.8% CT, 1.5% TT; p=0.004) and between mutant (TT and CT) and wild-type genotypes (CC) (p=0.001). The mutant genotype was associated with a risk of hypertension (OR 2.1; 95% CI 1.3–3.5) when adjusted for age, body mass index, waist circumference, and diabetes mellitus. The mutant of the MTHFR C677T gene increases the risk of hypertension in rural Indonesian-Sundanese population. These findings may be used in future studies to evaluate the effect of riboflavin supplementation in this population.
Highlights
Hypertension is a multifactorial disease influenced by interaction of genetic, environmental, and demographic factors [1]
Cases had a higher number of diabetes mellitus than controls, but the difference was not statistically significant (Table 1)
To the best of our knowledge, this is the first study to investigate the association between Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with hypertension in Indonesia, especially in a rural Sundanese population. e major finding of this study was that the presence of MTHFR variants was an independent predictor of hypertension
Summary
Hypertension is a multifactorial disease influenced by interaction of genetic, environmental, and demographic factors [1]. Latest evidence showed that approximately 30%–50% of blood pressure variation was contributed by genetic factors [2]. Single-nucleotide polymorphism of the MTHFR C677T gene from alanine to valine reduces enzymatic activity, which, in turn, decreases the concentration of 5-methyltetrahydrofolate, which regulates the endothelial cells and nitrite oxides (NO) involved in the pathophysiology of hypertension [3, 4]. E reduced activity of MTHFR enzyme is related to the reduced concentration of its cofactor, riboflavin or vitamin B2. Supplementation of this widely available and affordable vitamin stabilizes the enzyme by increasing the endothelial functions and NO availability, especially in genotype variants [10]. Several randomized control trials showed significant blood pressure control in this variant population even after several years of follow-up [11,12,13]
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