Association between Paraoxonase 1 (PON1) Polymorphisms and the Risk of Acute Coronary Syndrome in a North African Population

<div><p>The purpose of the present study was to investigate the distribution of PON1 Q192R and L55M polymorphisms and activities in a North African population and to determine their association with cardiovascular complications. The prevalence of the QQ, QR, RR, LL, LM, and MM genotypes in the study population was 55.4%, 34.09%, 9.83%, 41.97%, 48.20%, and 9.83% respectively. The Q, R, L, and M alleles had a gene frequency of 0.755, 0.245, 0.67, and 0.33, respectively. The PON1 192 RR genotype was significantly more prevalent among ACS patients than among healthy subjects. There was a 4.33-fold increase in the risk of ACS in subjects presenting the PON1 192 RR genotype compared to those with the QQ genotype (OR=4.33; 95% CI=1.27–17.7). There was a significantly different distribution of PON1 L55M in the ACS patient groups (UA, STEMI, NSTEMI). Moreover, individuals presenting the PON1 55MM genotype present a higher risk for ACS than those with LL genotype (OR=3.69; 95% CI=1.61–11.80). Paraoxonase activities were significantly lower in coronary patients than in healthy subjects. The decrease in PON1 activity was inversely correlated with the number of concomitant risk factors for CVD (r=0.57, p<0.0001). The results of the present study suggested that the PON1 R and M alleles may play a role in the pathogenesis of cardiac ischemia in our North African population and that a decrease in PON1 activity may be a valuable marker for monitoring the development of the atherosclerosis process and the associated cardiovascular complications.</p></div

Correlation between PON1 paraoxonase activity and the number of concomitant risk factors for CVD.

<p>CVD risk factors: diabetes, obesity, high arterial blood pressure, alcohol, smoking, and family history. A Pearson correlation analysis was performed to assess the association between CVD risk factors and PON1 paraoxonase activity. H: Healthy, ACS: Acute Coronary Syndrome.</p

PON1 phenotypic distribution, activities, and oxidative stress markers in the healthy subjects and ACS patients.

<p>Values are means ± SEM, unless indicated otherwise. The Student’s <i>t-test</i> and χ2 test (for PON1 phenotypic distribution) were used. Significance was established by comparing the results from the ACS patients with those from the healthy subjects:</p><p>**p<0.01,</p><p>***p<0.001,</p><p>****p<0.0001.</p><p>PON1 phenotypic distribution, activities, and oxidative stress markers in the healthy subjects and ACS patients.</p

HANDBOOK OF RESEARCH METHODS IN CLINICAL-PSYCHOLOGY - KENDALL,PC, BUTCHER,JN

<p>The PON1 L55M genotype was determined by RT-PCR. PON1 paraoxonase activity was determined by measuring paraoxon absorbance at 412 nm. Results are expressed as means ± SEM. ****p<0.0001 for comparison between ACS patients and healthy subjects with the same PON1 L55M polymorphism.</p

PON1 55 and PON1 192 carrier frequencies of the 205 ACS patients.

<p>χ² = 2.83, d.f. = 2, <i>p</i> = 0.09 for comparisons between the ACS diagnosis and PON192 carriers, and χ² = 17.2, d.f. = 2, <i>p</i> = 0.0002 for comparisons between the ACS diagnosis and PON55 carriers</p><p>PON1 55 and PON1 192 carrier frequencies of the 205 ACS patients.</p

PON1 arylesterase activity in the healthy subjects and the ACS patients and based on their PON1 192 genotype.

<p>The PON1 Q192R genotype was determined by RT-PCR. PON1 arylesterase activity was measured by the increase in absorbance at 270 using phenylacetate as a substrate. Results are expressed as means ± SEM. ** p<0.001 and ****p<0.0001 for the ACS patients compared to the healthy subjects with the same PON1 Q192R polymorphism.</p

Comparison of the triglyceride levels of healthy subjects and ACS patients as a function of PON1 Q192R polymorphism.

<p>***p<0.0001 and **** p<0.001 compared with the healthy subjects with the same PON1 Q192R polymorphism.</p

Genotype and allele frequencies of the L55M polymorphism.

<p>Contribution of the PON1 L192M polymorphism to ACS was estimated by logistic regression for unmatched data to obtain odds ratios for the PON1 L192M polymorphisms. <b><i>Italics bold indicate the odds ratios adjusted for age</i>, <i>sex</i>, <i>BMI and HDL cholesterol</i>.</b></p><p>*(%) of the entire population (healthy subjects and ACS patients)</p><p>Genotype and allele frequencies of the L55M polymorphism.</p

Comparison of the triglyceride levels of healthy subjects and ACS patients as a function of PON1 L55M polymorphism.

<p>**** p<0.001 compared with the healthy subjects with the same PON1 L55M polymorphism.</p

PON1 genotypic distribution and odds ratios of the genotype and alleles of the Q192R polymorphism in the healthy subjects and the ACS patients.

<p>*n.s., not significant</p><p>Contribution of the PON1 Q192R polymorphism to ACS was estimated by logistic regression for unmatched data to obtain odds ratios for the PON1 Q192R polymorphisms. <b><i>Italics bold indicate the odds ratios adjusted for age</i>, <i>sex</i>, <i>BMI and HDL cholesterol</i>.</b></p><p>PON1 genotypic distribution and odds ratios of the genotype and alleles of the Q192R polymorphism in the healthy subjects and the ACS patients.</p