MTHFR C677T polymorphism and its homocysteine-driven effect on blood pressure.

Abstract

High blood pressure (hypertension) is the single most important modifiable risk factor for ischemic stroke (1) and is defined as systolic blood pressure ≥140 mmHg and/or as diastolic blood pressure ≥90 mmHg. Data suggest that elevated homocysteine is an independent risk factor for hypertension (2). Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been found to be associated with increased homocysteine (>15 μmol/L) and hypertension (3), although associations are conflicting (4). Interrelationship among MTHFR C677T, homocysteine, and blood pressure is less understood. We examined the effect of MTHFR C677T polymorphism and hyperhomocysteinemia on blood pressure in a North Eastern population with East Asian ancestry. A total of 1142 individuals aged 35–75 years (unrelated up to first cousin) were recruited and fasting lipids and glucose, height, weight, waist and hip circumferences, blood pressure, and homocysteine (n = 200) were measured, and MTHFR C677T was genotyped after taking their written informed consent. Two hundred forty-eight individuals were identified with hypertension, and a crosssectional design was formulated with their 248 age and gender-matched controls (normotensives). Individuals having TT genotype of MTHFR C677T had significantly higher blood pressure than those having CC genotype. TT genotype and elevated homocysteine levels between 10 to 15 μmol/L and above showed significant eightfold and threefold increased risks, respectively, for hypertension. Hyperhomocysteinemia and MTHFR C677T showed significant increased risk even after controlling for probable confounders. We, therefore, conclude that MTHFR 677TT genotype and elevated homocysteine levels (even in the upper limits of the normal range of 5–15 μmol/L) are significantly associated with hypertension particularly in the present population, regardless of age and gender. Although the study did not assess the association of MTHFR C677T and increased homocysteine levels directly with stroke, the study highlights a homocysteine-driven effect of MTHFR C677T on blood pressure that is an important risk factor for stroke and various stroke-related anomalies.