Homocysteine, the methylenetetrahydrofolate reductase 677C>T polymorphism and hypertension: Effect modifiers by lifestyle factors and population subgroups

Abstract

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18-75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/ d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association (&beeta; standardised regression coefficients) was stronger in male smokers (0-52, P < 0-001) compared with non-smokers (0-21, P = 0-001) and weaker in participants aged >50 years (0-19, P = 0-007) compared with ≤50 years (0-31, P < 0-001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1-9; 95 % CI 1-2, 3-0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4-1; 95 % CI 1-0, 16-9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6-2; 95 % CI 1-0, 38-7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype-hypertension association was confined to adults aged ≤50 years.