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

Identifier:  imarina:6159135

Handle: https://hdl.handle.net/20.500.11797/imarina6159135

Authors:  Ornosa-Martín, G; Fernandez-Ballart, JD; Ceruelo, S; Ríos, L; Ueland, PM; Meyer, K; Murphy, MM

Abstract:
© The Authors 2020. Evidence linking fasting plasma total homocysteine (tHcy), 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 was conducted in 788 adults, aged 18-75 years, randomly selected from 3 Catalonian town population registers. Fasting plasma folate, cobalamin, total homocysteine (tHcy), red blood cell folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677 C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded.Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/day) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association (β standardised regression coefficients) was stronger in male smokers (0.52, P < 0.001) compared to nonsmokers (0.21, P = 0.001) and weaker in participants >50 (0.19, P = 0.007) compared to ≤50 years (0.31, P < 0.001). Hypertension was more probable in the 3rd tHcy tertile compared to the other tertiles [OR 1.9 (1.2, 3.0)], and in participants ≤50 years, for the MTHFR 677TT genotype compared to the CC genotype [OR 4.1 (1.0, 16.9)]. EGRAC was associated with increased probability of hypertension in participants >50 years [OR 6.2 (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 ≤50 years.