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).
In the past few years, the Paraoxonase multigene family (<i>PON1, PON2, PON3</i>) has been shown to play an important role in pathogenesis of cardiovascular disorders including coronary artery disease (CAD).
As studies are lacking in North-West Indian Punjabi's, a distinct ethnic group with high incidence of CAD, we determined PON1 activity, genotypes and haplotypes in this population and correlated them with the risk of CAD.
We aimed to systematically investigate the role of genetic variations and DNA methylation of the PON1 CpG island promoter on the clinical outcomes of dual antiplatelet therapy for patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI).
Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for coronary artery disease, but the results of genetic association studies on the related phenotype of ischemic stroke are inconclusive.
In summary, this meta-analysis proved that PON1rs854560 polymorphism could be used to identify individual with elevated susceptibility to IS, whereas rs662 polymorphism could be used to identify individual with elevated susceptibility to CAD.
Therefore, we studied the human paraoxonase gene (PON1) polymorphism in Turkish patients with CAD by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP).
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).
Furthermore, a Receiver Operating Characteristic Curve (ROC) analysis indicated that a PON1 activity cut-off point of 330 U/L could predict CAD with a sensitivity of 52% and a specificity of 65%.
HDL-associated paraoxonase (PON1) reduces oxidation of lipids in LDL, and activity is inversely related to coronary heart disease risk with a beneficial effect on the development of atherosclerosis.
The present study revealed an association between carrier state of Q allele of PON1 gene and coronary artery disease as well as synergistic effects between genotype and some conventional risk factors, mainly smoking and elevated level of total cholesterol.
We illustrate the proposed method through three meta-analyses for comparison of prostate cancer treatment, for the association between paraoxonase 1 activities and coronary heart disease, and for the association between homocysteine level and coronary heart disease.
Effect of statin therapy on plasma high-density lipoprotein-cholesterol levels is modified by paraoxonase 1 in Chinese patients with coronary heart disease.
The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation.
A common polymorphism at codon 192(Q/R) of the PON 1 gene has been shown to be associated with an adverse lipoprotein profile and increased coronary artery disease (CAD) risk.
Finally, we suggest directions for the future that might elucidate the role of the PON genetic polymorphisms in this potentially important function of PON(s) and the role in coronary heart disease and other related diseases.
The links between PON1 and Hcy in relation to pathological states such as coronary artery disease, stroke, diabetic mellitus, kidney failure and Alzheimer's disease that emerge from recent studies are the topics of this review.
Studies have been conducted to evaluate the possible "protective" role of PON, and especially the influence of the Arg-->Gln 192 polymorphism, in coronary artery disease.