The Effect of Methylenetetrahydrofolate Reductase C677T Common Variant on Hypertensive Risk Is Not Solely Explained by Increased Plasma Homocysteine Values

• Published in: Clinical and experimental hypertension (1993) 2003-05, Vol.25 (4), p.209-220
• Main Authors: Rodríguez-Esparragón, Francisco, Hernández-Perera, Octavio, Rodríguez-Pérez, José C., Anabitarte, Aránzazu, Díaz-Cremades, Juan M., Losada, Antonio, Fiuza, Dolores, Hernández, Enrique, Yunis, Carla, Ferrario, Carlos M.
• Format: Article
• Language: English
• Subjects: Aged; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Blood Pressure - genetics; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Female; Genetic Predisposition to Disease - epidemiology; Genotype; Homocysteine; Homocysteine - blood; Humans; Hyperhomocysteinemia - blood; Hyperhomocysteinemia - epidemiology; Hyperhomocysteinemia - genetics; Hypertension; Hypertension - blood; Hypertension - epidemiology; Hypertension - genetics; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; MTHFR gene; Multivariate Analysis; Oxidoreductases Acting on CH-NH Group Donors - genetics; Point Mutation; Polymorphism; Polymorphism, Genetic; Risk Factors
• ISSN: 1064-1963; 1525-6006
• DOI: 10.1081/CEH-120020391

The C677T transition of methylenetetrahydrofolate reductase (MTHFR) gene causes a moderate increase in total plasma homocysteine (tHcy). We studied the effect of MTHFR TT homozygosity and mild hyperhomocysteinemia on arterial hypertension. Normotensive controls (n = 223) and hypertensive subjects (n = 235) were matched for age, gender, and history of cardiovascular disease. Homocysteine levels were measured by a fluorescense polarization immunoassay method. Methylenetetrahydrofolate reductase genotypes were determined by polymerase chain reaction and restriction fragment analysis. Hypertensives showed elevated tHcy compared to normotensive group in men (P = 0.039). Homocysteine values higher than 15 µmol L were associated with increased hypertensive risk in the male population [odds ratios (OR) = 1.63; 95% confidence interval (CI) = 1.06-2.52; P = 0.027]. In multivariate analysis, TT genotype was associated with an increased risk of hypertension in males (OR = 2.27; 95% CI = 1.12-4.60; P = 0.022). An increased hypertensive risk was observed in those TT males with tHcy levels higher than 15 µmol L (OR = 2.78; 95% CI = 1.05-7.3; P = 0.032) but not in those non-TT males with tHcy levels higher than 15 µmol L (P = 0.33). Our findings do not support the possibility that mild hyperhomocysteinemia may solely account for the hypertensive risk associated to the TT genotype.