Addressing the link between paraoxonase-1 gene variants and the incidence of early onset myocardial infarction

Abstract

Introduction: The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was to investigate the association between PON1 Q192R polymorphism, PON1 phenotypes and the incidence of early-onset acute myocardial infarction (AMI) in Egyptians.

Material and methods: The study subjects consisted of 102 AMI patients and 72 age-matched healthy controls. Genotyping and enzyme activities were determined using PCR-RFLP and kinetic spectrophotometric assays, respectively.

Results: The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02%, RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%). Allele frequencies were also significantly different between patients (Q = 62.75%, R = 37.25%) and controls (Q = 79.17%, R = 20.83%). The genotypes QR and RR showed higher risk for AMI compared to the homozygous QQ (odds ratio (OR) = 3.231, p < 0.001). The average PON/ARE ratio in MI patients (1.187 ±0.1) did not differ significantly from controls (1.118 ±0.26). However, it showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (p = 0.0002) and controls (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (p < 0.0001).

Conclusions: PON1 192R allele represents an independent risk factor for early-onset AMI in Egyptians, and PON1 Q192R polymorphism modulates the paraoxonase phenotype.

Keywords: Egyptians; PON polymorphism; acute myocardial infarction; arylesterase; paraoxonase.

Figure 1

Possible Q192R polymorphism outcomes

Figure 2

The PON1 genotype distribution in MI and controls. The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02% and RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%) (Mann-Whitney test, p = 0.0006)

Figure 3

The PON1 allele frequencies in MI and controls. The allele frequencies were significantly different between AMI patients (Q = 62.75% and R = 37.25%) and controls (Q = 79.17% and R = 20.83%) (Mann-Whitney test, p = 0.0011)

Figure 4

The PON activities among different genotypes in MI patients and controls. There was a significant difference in the PON activities among the different genotypes in both AMI patients (QQ = 60.88 ±6.36, QR = 69.66 ±6.56 and RR = 222.7 ±20.75 U/ml) (Kruskal-Wallis; p < 0.0001) and control subjects (QQ = 65.58 ±7.9, QR = 101.4 ±14.15 and RR = 206.6 ±53.65 U/ml) (Kruskal-Wallis; p = 0.0025)

Figure 5

The ARE activities among different genotypes in MI patients and controls. No significant difference was observed in the ARE activities among the different genotypes in both AMI patients (QQ = 79.56 ±6.62, QR = 69.08 ±4.73 and RR = 95.2 ±11.38 U/ml) (Kruskal-Wallis; p = 0.1170) and control subjects (QQ = 106.9 ±6.86, QR = 101.5 ±10.54 and RR = 86.28 ±31.62 U/ml) (Kruskal-Wallis; p = 0.8092)

Figure 6

PON/ARE ratios among different genotypes in MI patients and controls. PON/ARE ratios showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (Kruskal-Wallis; p = 0.0002) and control subjects (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (Kruskal- Wallis; p < 0.0001)