Promoter polymorphism T(-107)C of the paraoxonase PON1 gene is a risk factor for coronary heart disease in type 2 diabetic patients

Details

Serval ID
serval:BIB_9033875422BC
Type
Article: article from journal or magazin.
Collection
Publications
Title
Promoter polymorphism T(-107)C of the paraoxonase PON1 gene is a risk factor for coronary heart disease in type 2 diabetic patients
Journal
Diabetes
Author(s)
James  R. W., Leviev  I., Ruiz  J., Passa  P., Froguel  P., Garin  M. C.
ISSN
0012-1797
Publication state
Published
Issued date
08/2000
Volume
49
Number
8
Pages
1390-3
Notes
20378145
0012-1797
Journal Article --- Old month value: Aug --- Old uritopublisher value: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10923642
Abstract
The serum enzyme paraoxonase (PON) protects LDLs from oxidative stress. We recently identified promoter polymorphisms of the PON gene that strongly affect gene expression and serum levels of the enzyme. The present study tested the hypothesis that promoter polymorphism T(-107)C could be a risk factor for vascular disease in type 2 diabetic patients by virtue of its ability to modulate serum concentrations of the antioxidant enzyme. The low-expressor genotype (TT) was associated with significantly lower serum PON concentrations, and it was over-represented in type 2 diabetic patients with coronary heart disease (CHD) (TT vs. TC+CC: odds ratio [OR] 1.64 [95% CI 1.03-2.61], P < 0.05). The association of the low-expressor genotype with an increased risk of disease was independent of other risk factors, including the coding region Q191R polymorphism (OR 2.12 [95% CI 1.19-3.70], P = 0.01). However, an interaction of the promoter polymorphism with the Q191R polymorphism, which was previously identified as an independent risk factor, was observed. The low-expressor promoter allele (-107T) associated with the high-risk 191R allele showed a lower-than-expected level of risk (OR 2.21 vs. the expected 4.76). The data are consistent with the hypothesis that low expression of the antioxidant enzyme PON increases the risk of CHD. Moreover, the promoter polymorphism appears to have a modulating effect on risk that is associated with the coding region polymorphism Q191R. This study indicates a strong genetic component to the antioxidant capacity of HDLs.
Keywords
Blood Pressure Coronary Disease/*epidemiology/*genetics Diabetes Mellitus, Non-Insulin-Dependent/enzymology/*genetics/physiopathology Diabetic Angiopathies/*genetics Esterases/blood/*genetics Female Genotype Human Lipids/blood Male Middle Age Point Mutation *Polymorphism (Genetics) *Promoter Regions (Genetics) Risk Factors Smoking Support, Non-U.S. Gov't
Pubmed
Web of science
Open Access
Yes
Create date
03/03/2008 15:16
Last modification date
20/08/2019 14:53
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