The One-Carbon metabolic network, the L-Arginine pathway and hypertension in adults and during pregnancy.

Identifier:  TDX:3970

Handle: https://hdl.handle.net/20.500.11797/TDX3970

Authors:  Ramos Rodríguez, Carla

Abstract:
Impaired One-Carbon metabolism (1CM) has been associated with hypertension and pregnancy-induced hypertension, although the mechanism is unknown. During homocysteine remethylation, S-adenosylmethionine donates methyl groups to methylate L-Arginine, creating ADMA and SDMA, which impair the conversion of L-Arginine to nitric oxide (NO) by eNOS. This has been associated with endothelial dysfunction, as NO is a vasodilator. In a representative population of 788 adults tHcy, but not the MTHFR C677T genotype, was associated with ADMA and SDMA. ADMA, the L-Arginine/ADMA Ratio and the NOS G894T genotype variant were associated with hypertension in adults over 50 years of age. In the Reus-Tarragona Birth Cohort, 810 mothers at <12 weeks of gestation were recruited. First-trimester maternal plasma concentrations of ADMA and SDMA were higher in the highest first-trimester tHcy tertile compared with the lowest, and lower in participants with the MTHFR TT versus CC genotype. The ADMA/SDMA Ratio in first- trimester maternal plasma was associated with an increased risk of pregnancy-induced hypertension. The 416 participating fathers with tHcy in the highest tertile had higher plasma ADMA and SDMA concentrations compared with the lowest tertiles. Paternal ADMA and SDMA concentrations did not differ between MTHFR C677T genotypes.