Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes.

Détails

ID Serval
serval:BIB_1976
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes.
Périodique
Journal of Clinical Investigation
Auteur⸱e⸱s
Garin M.C., James R.W., Dussoix P., Blanché H., Passa P., Froguel P., Ruiz J.
ISSN
0021-9738 (Print)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
1997
Volume
99
Numéro
1
Pages
62-66
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Paraoxonase was identified as a genetic risk factor for cardiovascular disease (CVD) in recent studies focusing on a polymorphism affecting position 191. A second polymorphism of the paraoxonase gene affects position 54 and involves a methionine (M allele) to leucine (L allele) change. It was investigated in diabetic patients (n = 408) with and without vascular disease. There were highly significant differences in plasma concentrations and activities of paraoxonase between genotypes defined by the 54 polymorphism: MMAA, MLAA, LLAA; protein, 65.3+/-18.0, 77.9+/-18.0, 93.5+/-26.0 microg/ml; P < 0.0001: activity (phenylacetate), 48.6+/-13.5, 64.1+/-14.5, 68.1+/-13.0 U/ml; P < 0.0001. The 191 variant had little impact on paraoxonase concentrations. Homozygosity for the L allele was an independent risk factor for CVD (odds ratio 1.98 (1.07-3.83); P = 0.031). A linkage disequilibrium (P < 0.0001) was apparent between the mutations giving rise to leucine and arginine at positions 54 and 191, respectively. The study underlines that susceptibility to CVD correlates with high activity paraoxonase alleles. The 54 polymorphism would appear to be of central importance to paraoxonase function by virtue of its association with modulated concentrations. The latter could explain the association between both the 54 and 191 polymorphisms and CVD.
Mots-clé
Aged, Alleles, Arginine/genetics, Aryldialkylphosphatase, Cardiovascular Diseases/complications, Cardiovascular Diseases/genetics, Cholesterol/metabolism, DNA/analysis, Diabetes Mellitus, Type 2/complications, Esterases/genetics, Esterases/metabolism, Female, Gene Expression Regulation, Genetic Linkage, Humans, Leucine/genetics, Lipoproteins, HDL/metabolism, Male, Middle Aged, Odds Ratio, Point Mutation, Polymorphism, Genetic, Risk Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 12:14
Dernière modification de la notice
20/08/2019 12:50
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