Paraoxonase activity, but not haplotype utilizing the linkage disequilibrium structure, predicts vascular disease.
Arterioscler Thromb Vasc Biol
; 23(8): 1465-71, 2003 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-12805074
ABSTRACT
OBJECTIVE:
The effects of paraoxonase (PON1) activity and of genetic variation in the PON1 promoter and coding region on carotid artery disease (CAAD) were investigated. METHODS ANDRESULTS:
We identified functional promoter polymorphisms and examined their effects in a cohort with and without CAAD. We used the full sequences in 23 white subjects to determine the linkage disequilibrium (LD) structure of the PON1 region and to direct the grouping of haplotypes for disease association testing. There are several discrete regions of the PON1 gene with strong local LD, but the useful levels of LD do not extend across the entire gene. Indeed, PON1-162/-108/55/192 haplotype did not predict additional variation in PON1 activities compared with the 4 genotypes separately. PON1 hydrolysis activity predicted CAAD status, but this was not attributable to the promoter or coding region polymorphisms or haplotype or to the effects of smoking or statin use on PON1 activity.CONCLUSIONS:
PON1 does not have LD across the gene, and use of haplotypes in association studies should consider the LD structure. PON1 activity predicts CAAD, yet 4 functional polymorphisms do not. Additional investigations of genetic and environmental factors that influence PON1 activity as a risk factor for vascular disease are warranted.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de las Arterias Carótidas
/
Arildialquilfosfatasa
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos