The AA genotype of the rs854560 SNPs of the PON1 gene is associated with increased mortality in patients after myocardial infarction in the subpopulation of patients with lowered eGFR.
A genome-wide association study identified distinct single nucleotide polymorphisms within the PON-1 gene that were highly significantly associated with serum paraoxonase (1.18×10(-303)) or arylesterase (4.99×10(-116)) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort (n=2136) or history of either coronary artery disease or myocardial infarction in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis consortium (n≈80 000 subjects).
We tested the effects of PON1 polymorphisms on clopidogrel pharmacokinetics and pharmacodynamics and the occurrence of cardiovascular outcomes in young post-myocardial infarction (MI) patients treated with clopidogrel.
The paraoxonase (PON1) polymorphisms, Leu55Met and Gln192Arg, modulate intima-medial artery thickening, prognosis of cardiovascular stroke, and renal failure in other diseases.
The present study showed a significant and independent association between the PON1Q192R polymorphism (presence of R allele) and MI in the Tunisian population.
Consistently, high-risk genotypes of the PON1Q192R and eNOS E298D polymorphisms were significantly associated with onset of a first MI at age <50 years (adjusted odds ratio 1.70, p = 0.005, adjusted odds ratio 2.15, p = 0.01, respectively).
Our data suggest that PON1Q192R polymorphism was not independently associated with MI but further increased the risk of MI among the subjects with DM, obesity, or both, the conditions associated with high oxidative stress.
However, the frequency of the PON1-192-RR genotype tended to be lower in CAD subjects than in controls (2% vs 10.0%, p = 0.057) and higher in MI subjects that in CAD subjects (10.9% vs 2.0%, p = 0.001).
We evaluated three PON polymorphisms (PON1Leu55Met and Gln192Arg; PON2 Ser311Cys) as possible risk factors for coronary atherosclerotic disease (CAD) and/or its main thrombotic complication, myocardial infarction (MI).
Because PON1-192 polymorphism strongly influences PON1 activity toward paraoxon, we tested the hypothesis that this polymorphism may modulate the myocardial infarction (MI) risk associated with low HDL cholesterol concentrations.
We conclude that the risk of MI associated with smoking appears to be increased in subjects who are homozygous for the low-activity PON1 QQ genotype compared with R carriers, and this risk seems to be time- and dose-dependent.