Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with coronary artery disease.
Oxidative damage is a major cause of atherosclerosis. Since human paraoxonase has been postulated as a factor which plays a role in protection from low density lipoprotein oxidation, recent studies have dealt with the impact of hereditary PON1 gene polymorphisms as risk factors for coronary artery disease (CAD). The results from these studies are conflicting. In a case-control study, 1000 Caucasian patients with angiographically confirmed CAD were recruited and matched by age and gender to 1000 control individuals. PON1 mutations in codons 55 and 192 were evaluated by polymerase chain reaction-restriction fragment length polymorphism and allocated to defined haplotypes *1 (55L/192Q), *2 (55L/192R), and *3 (55M/192Q). Frequency of PON1 genotypes without any mutation (PON1*1/*1, wild-type) in CAD cases was 16.9% versus 17.1% in control individuals. PON1*2/*2 showed a frequency of 6.6% versus 7.3% (P = 0.68 compared to wild-type), and PON1*3/3 occurred in 11.8% in CAD cases versus 10.3% among control individuals (P = 0.40). There was also no difference in the distribution of carriers heterozygous for *2 or *3 among cases and control individuals. A haplotype containing both mutations 55M and 192R was not observed. None of the investigated genotypes demonstrated association with early manifestation, severity of disease, acute coronary syndromes, or myocardial infarction. Logistic regression analysis with adjustment for age, gender, diabetes, hypertension, hypercholesterolemia and smoking revealed no evidence of increased coronary risk associated with PON1 genotypes. These results suggest that PON1 polymorphisms are not major genetic determinants of CAD.
Cascorbi
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I
Institute of Clinical Pharmacology, University Clinic Charité, Humboldt University, Berlin, Germany. ingolf.cascorbi@charite.de
Laule
M
M
Mrozikiewicz
P M
PM
Mrozikiewicz
A
A
Andel
C
C
Baumann
G
G
Roots
I
I
Stangl
K
K
D000483:Alleles; D043303:Aryldialkylphosphatase; D001483:Base Sequence; D003327:Coronary Disease / Q000235:genetics*; D017931:DNA Primers; D004950:Esterases / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009154:Mutation
D017931:DNA Primers; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human