Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia.

Abstract:

: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.

journal_name

J Lipid Res

authors

van Himbergen TM,Roest M,de Graaf J,Jansen EH,Hattori H,Kastelein JJ,Voorbij HA,Stalenhoef AF,van Tits LJ

doi

10.1194/jlr.M400052-JLR200

keywords:

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

445-51

issue

3

eissn

0022-2275

issn

1539-7262

pii

M400052-JLR200

journal_volume

46

pub_type

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