TY - JOUR
T1 - B-vitamin levels and genetics of hyperhomocysteinemia are not associated with arterial stiffness
AU - van Dijk, S.C.
AU - Enneman, A.W.
AU - van Meurs, J.
AU - Swart, K.M.A.
AU - Ham, A.H.
AU - van Wijngaarden, J.P.
AU - Brouwer-Brolsma, E.M.
AU - van der Zwaluw, N.L.
AU - van Schoor, N.M.
AU - Dhonukshe-Rutten, R.A.M.
AU - de Groot, L.C.P.G.
AU - Lips, P.T.A.M.
AU - Uitterlinden, A. G.
AU - Blom, H.J.
AU - Geleijnse, J.M.
AU - Feskens, E.
AU - de Jongh, R.T.
AU - Smulders, Y.M.
AU - van den Meiracker, A.H.
AU - Mattace-Raso, F.U.S.
AU - van der Velde, N.
PY - 2014
Y1 - 2014
N2 - Hyperhomocysteinemia is associated with arterial stiffness, but underlying pathophysiological mechanisms explaining this association are to be revealed. This study was aimed to explore two potential pathways concerning the one-carbon metabolism. A potential causal effect of homocysteine was explored using a genetic risk score reflecting an individual's risk of having a long-term elevated plasma homocysteine level and also associations with B-vitamin levels were investigated. Baseline cross-sectional data of the B-PROOF study were used. In the cardiovascular subgroup (n = 567, 56% male, age 72.6 ± 5.6 yrs) pulse wave velocity (PWV) was determined using applanation tonometry. Plasma concentrations of vitamin B12, folate, methylmalonic acid (MMA) and holo transcobalamin (holoTC) were assessed and the genetic risk score was based on 13 SNPs being associated with elevated plasma homocysteine. Associations were examined using multivariable linear regression analysis. B-vitamin levels were not associated with PWV. The genetic risk score was also not associated with PWV. However, the homocysteine-gene interaction was significant (p < 0.001) in the association of the genetic risk score and PWV. Participants with the lowest genetic risk of having long-term elevated homocysteine levels, but with higher measured homocysteine levels, had the highest PWV levels. Homocysteine is unlikely to be causally related to arterial stiffness, because there was no association with genetic variants causing hyperhomocysteinemia, whereas non-genetically determined hyperhomocysteinemia was associated with arterial stiffness. Moreover, the association between homocysteine and arterial stiffness was not mediated by B-vitamins. Possibly, high plasma homocysteine levels reflect an unidentified factor, that causes increased arterial stiffness
AB - Hyperhomocysteinemia is associated with arterial stiffness, but underlying pathophysiological mechanisms explaining this association are to be revealed. This study was aimed to explore two potential pathways concerning the one-carbon metabolism. A potential causal effect of homocysteine was explored using a genetic risk score reflecting an individual's risk of having a long-term elevated plasma homocysteine level and also associations with B-vitamin levels were investigated. Baseline cross-sectional data of the B-PROOF study were used. In the cardiovascular subgroup (n = 567, 56% male, age 72.6 ± 5.6 yrs) pulse wave velocity (PWV) was determined using applanation tonometry. Plasma concentrations of vitamin B12, folate, methylmalonic acid (MMA) and holo transcobalamin (holoTC) were assessed and the genetic risk score was based on 13 SNPs being associated with elevated plasma homocysteine. Associations were examined using multivariable linear regression analysis. B-vitamin levels were not associated with PWV. The genetic risk score was also not associated with PWV. However, the homocysteine-gene interaction was significant (p < 0.001) in the association of the genetic risk score and PWV. Participants with the lowest genetic risk of having long-term elevated homocysteine levels, but with higher measured homocysteine levels, had the highest PWV levels. Homocysteine is unlikely to be causally related to arterial stiffness, because there was no association with genetic variants causing hyperhomocysteinemia, whereas non-genetically determined hyperhomocysteinemia was associated with arterial stiffness. Moreover, the association between homocysteine and arterial stiffness was not mediated by B-vitamins. Possibly, high plasma homocysteine levels reflect an unidentified factor, that causes increased arterial stiffness
U2 - https://doi.org/10.1016/j.numecd.2014.01.008
DO - https://doi.org/10.1016/j.numecd.2014.01.008
M3 - Article
C2 - 24656138
SN - 0939-4753
VL - 24
SP - 760
EP - 766
JO - Nutrition, Metabolism and Cardiovascular Diseases
JF - Nutrition, Metabolism and Cardiovascular Diseases
IS - 7
ER -
