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Variation at the paraoxonase gene locus contributes to carotid arterial wall thickness in subjects with familial hypercholesterolemia
- Source :
-
Clinical Biochemistry . Feb2005, Vol. 38 Issue 2, p123-127. 5p. - Publication Year :
- 2005
-
Abstract
- Abstract: Objectives:: Paraoxonase (PON1) is a potent enzyme, physically associated with the high-density lipoprotein particle. PON1 may protect against cardiovascular disease (CVD), since it is capable of hydrolyzing oxidized LDL-cholesterol, thereby negating the detrimental effects of this lipoprotein on the arterial wall. Design and methods:: In 187 patients with familial hypercholesterolemia, we studied the seven most common single nucleotide polymorphisms (SNPs) in both the coding and promoter sequences of PON1 (L55M, Q192R, T-107C, C-126G, G-162A, G-824A, and C-907G) in terms of PON1 activity and intima media thickness (IMT) of the carotid arterial wall, a validated surrogate marker for CVD. Results:: In concordance with several previous studies, we observed that the L55M, T-107C, G-162A, G-824A, and C-907G SNPs conferred PON1 activity towards phenylacetate, while this was not the case for the Q192R and C-126G SNPs. Importantly, in a multivariate regression analysis, G-824A proved to be an independent predictor of carotid IMT. Additionally, the two fully discordant homozygous haplotypes, C-907/G-824/G-162/C-126/T-107/55M versus -907G/-824A/-162A/-126G/-107C/L55, differed by 22% in carotid IMT (P = 0.007). Conclusions:: Genetic variation at the PON1 locus has a strong influence on PON1 activity as well as on carotid IMT. These data indicate that PON1 is indeed involved in the pathogenesis of atherosclerosis. Whether this also translates into a role for PON1 in the occurrence of CVD events needs to be confirmed by large prospective studies in the general population. [Copyright &y& Elsevier]
- Subjects :
- *PARAOXONASE
*LIPOPROTEINS
*CARDIOVASCULAR diseases
*HYPERCHOLESTEREMIA
Subjects
Details
- Language :
- English
- ISSN :
- 00099120
- Volume :
- 38
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Clinical Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16100980
- Full Text :
- https://doi.org/10.1016/j.clinbiochem.2004.10.005