We have examined the association of the PON1Q192R polymorphism with CHD in a large cohort of British women and combined the results from our cohort study with those from all other published studies.
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.
Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated enzyme involved in preventing the oxidation of low-density lipoprotein (LDL), and an association has been shown between two genetic polymorphisms in PON1 and the risk of coronary artery disease.
Many studies have examined the association between polymorphisms in the PON gene and risk of coronary heart disease (CHD), but the results have been inconsistent.
A common polymorphism of the PON1 gene, the PON1-192 genetic polymorphism, modulates PON1 activity and has been related in some studies to coronary heart disease.
We tested the clinical relevance of the PON1Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy.
The frequency of the R allele of PON1, which has been related to the risk of coronary heart disease, was significantly higher in Belfast (0.33) than in Toulouse (0.24; chi2 = 7.229, P = 0.0072).
Paraoxonase 1 (PON1) is located on HDL.Meta-analysis of clinical epidemiological investigations reveals a substantial association of low serum PON1 activity with coronary heart disease incidence independent of other risk factors including HDL cholesterol and apolipoprotein AI (apoAI).
These results indicate that lower PON1 activity and concentration and, therefore, the reduced ability to prevent LDL lipid peroxidation may be more important in determining the presence of CHD than paraoxonase genetic polymorphisms.
Our findings suggest blood THg and serum DHA+EPA levels have limited relationship to BP and PON-1 activity, and may not be important modulators of these known CHD risk factors in this population of avid seafood consumers.
Low PON1 enzyme activity or specific allelic polymorphisms seem to be associated with the risk of developing coronary artery disease or acute ischemic stroke (AIS).
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.
Heavy drinking was associated with an increased risk for CHD in black men with the PON1 QQ and CETP GG genotypes (PON1 hazard rate ratio [HRR]=17.3, 95% confidence interval [CI]: 1.76-170.2; CETP HRR=2.23, 95% CI: 1.01-4.91).
Significant interactions between two PON1 SNPs and smoking in relation to CHD risk were identified (adjusted P=0.012 for rs662; adjusted P=0.044 for rs3735590).