TY - JOUR
T1 - Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia
AU - van Himbergen, Thomas M.
AU - Roest, Mark
AU - de Graaf, Jacqueline
AU - Jansen, Eugène H. J. M.
AU - Hattori, Hiroaki
AU - Kastelein, John J. P.
AU - Voorbij, Hieronymus A. M.
AU - Stalenhoef, Anton F. H.
AU - van Tits, Lambertus J. H.
PY - 2005
Y1 - 2005
N2 - HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL ( OxLDL), subclinical inflammation [high-sensitive C-reactive protein (Hs-CRP)], and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, -107C/T, -162A/G, -824G/A, and -907G/C) were determined in 302 patients with familial hypercholesterolemia. PON1 activity was monitored by the hydrolysis rate of paraoxon, diazoxon, and phenyl acetate. PON1 levels, OxLDL, and Hs-CRP were determined using an immunoassay. The genetic variants of PON1 that were associated with high levels and activity of the enzyme were associated with higher HDL-C levels (P values for trend: 0.008, 0.020, 0.042, and 0.037 for L55M, Q192R, -107C/T, and -907G/C, respectively). In addition to the PON1 genotype, there was also a positive correlation between PON1 levels and activity and HDL-C (PON1 levels: r = 0.37, P <0.001; paraoxonase activity: r = 0.23, P = 0.01; diazoxonase activity: r = 0.29, P <0.001; arylesterase activity: r = 0.19, P = 0.03). Our observations support the hypothesis that both PON1 levels and activity preserve HDL-C in plasma
AB - HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL ( OxLDL), subclinical inflammation [high-sensitive C-reactive protein (Hs-CRP)], and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, -107C/T, -162A/G, -824G/A, and -907G/C) were determined in 302 patients with familial hypercholesterolemia. PON1 activity was monitored by the hydrolysis rate of paraoxon, diazoxon, and phenyl acetate. PON1 levels, OxLDL, and Hs-CRP were determined using an immunoassay. The genetic variants of PON1 that were associated with high levels and activity of the enzyme were associated with higher HDL-C levels (P values for trend: 0.008, 0.020, 0.042, and 0.037 for L55M, Q192R, -107C/T, and -907G/C, respectively). In addition to the PON1 genotype, there was also a positive correlation between PON1 levels and activity and HDL-C (PON1 levels: r = 0.37, P <0.001; paraoxonase activity: r = 0.23, P = 0.01; diazoxonase activity: r = 0.29, P <0.001; arylesterase activity: r = 0.19, P = 0.03). Our observations support the hypothesis that both PON1 levels and activity preserve HDL-C in plasma
U2 - https://doi.org/10.1194/jlr.M400052-JLR200
DO - https://doi.org/10.1194/jlr.M400052-JLR200
M3 - Article
C2 - 15576850
SN - 0022-2275
VL - 46
SP - 445
EP - 451
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 3
ER -