Paraoxonase 1 gene polymorphisms and dementia in humans.
Several clinical and epidemiological studies suggest that Alzheimer's disease (AD) and vascular dementia share common risk factors. Oxidative stress is one of these well recognized factors. It can result from an excess of free-radical activity and impaired antioxidant defenses. Paraoxonase (PON1), a component of high density lipoproteins, has antioxidative potential and was previously associated with an increased risk of cardiovascular diseases. The impact of two polymorphisms in PON1 (Gln192Arg associated with enzyme activity and T-107C associated with enzyme concentration) was examined in a case-control study. The two polymorphisms were independent risk factors for nonAD dementia, particularly in APOE-4 noncarriers. An at-'risk haplotype' could be constructed including the Gln192 and the T-107 alleles, suggesting that subjects at risk have lower plasma paraoxonase levels and this enzyme is less active.
Helbecque
Nicole
N
INSERM U508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille Cedex, France.
Cottel
Dominique
D
Codron
Valérie
V
Berr
Claudine
C
Amouyel
Philippe
P
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D003704:Dementia / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human