Haplotypes 192R-55L and 192R-55M may increase the risk of atherosclerosis requiring PCI/CABG, whereas the 192Q-55L haplotype may lower the risk.
Key Findings
Results
The PON1 haplotype 192R-55L was statistically significantly associated with a higher risk of coronary atherosclerosis requiring PCI or CABG.
OR = 2.06, 95% CI: 1.29–3.28, p = 0.0022
The study group included patients after PCI with stent implantation or patients who qualified for CABG, with stenoses of minimum 70% (n = 140)
The control group included individuals after coronarography without essential lesions in coronary vessels (n = 142)
The Q192R PON1 polymorphism was identified by PCR-RFLP in a Polish population
Results
The PON1 haplotype 192R-55M was statistically significantly associated with a higher risk of coronary atherosclerosis requiring PCI or CABG.
OR = 1.77, 95% CI: 1.17–2.69, p = 0.007
This association was identified in a retrospective study of 282 individuals of both sexes divided into study and control groups following coronarography
Both 192R-containing haplotypes (192R-55L and 192R-55M) showed elevated risk
Results
The PON1 haplotype 192Q-55L was associated with a 53% lower risk of coronary atherosclerosis requiring PCI or CABG.
OR = 0.47, 95% CI: 0.34–0.66, p = 0.000013
This was the strongest statistical association identified in the study
The protective effect of the 192Q-55L haplotype is consistent with the known role of PON1 in preventing LDL oxidation and atherosclerosis
Background
PON1 plays a protective role against atherosclerosis by preventing the oxidation of low-density lipoproteins (LDL), and polymorphisms Q192R and L55M affect enzyme activity and cardiovascular risk.
The Q192R and L55M polymorphisms in PON1 have been shown to affect enzyme activity
The study aimed to evaluate haplotype associations with severity of coronary atherosclerosis specifically in a Polish population
Coronary atherosclerosis severity was defined by stenoses of minimum 70% requiring PCI with stent implantation or CABG
Methods
The study was a retrospective design involving 282 individuals divided into two groups based on coronarography findings.
Study group: n = 140 patients after PCI with stent implantation or qualifying for CABG, with stenoses of minimum 70%
Control group: n = 142 individuals after coronarography without essential lesions in coronary vessels
Both sexes were included in the Polish population sample
Genotyping was performed using PCR-RFLP methodology for the Q192R PON1 polymorphism
What This Means
This research suggests that certain genetic variants of an enzyme called paraoxonase 1 (PON1) are linked to the severity of coronary artery disease. PON1 helps protect the heart by preventing the oxidation of 'bad' cholesterol (LDL), and different versions of the gene that codes for this enzyme — defined by two genetic variants called Q192R and L55M — appear to influence a person's risk of developing serious coronary artery blockages requiring medical procedures like stenting or bypass surgery. The study examined 282 Polish adults who had undergone coronary artery imaging, comparing those with significant blockages (at least 70% narrowing) to those with no significant blockages.
The researchers found that people carrying specific combinations (haplotypes) of these genetic variants faced meaningfully different risks. Those with the 192R-55L haplotype were about twice as likely, and those with the 192R-55M haplotype were about 77% more likely, to have severe coronary artery disease compared to those without these variants. In contrast, people with the 192Q-55L haplotype had a 53% lower risk of having severe coronary atherosclerosis — suggesting this genetic combination may be protective.
This research suggests that genetic testing for PON1 haplotypes could potentially help identify individuals at higher or lower risk of serious coronary artery disease. Understanding how specific gene variants affect enzyme function and cardiovascular risk may eventually contribute to more personalized approaches to heart disease prevention and risk assessment, though further research in larger and more diverse populations would be needed to confirm these findings.
Rychlik-Sych M, Barańska M, Dudarewicz M, Owczarek J. (2026). Association of PON1 Haplotypes (Q192R and L55M) with the Severity of Coronary Atherosclerosis.. International journal of molecular sciences. https://doi.org/10.3390/ijms27167241