Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score

Abstract

Objective: Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Materials and methods: Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Results: Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Conclusion: Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity. Arch Endocrinol Metab. 2016;60(5):426-35

Paraoxonase 1 and atherosclerosis‐related diseases

“…Results from different studies regarding the PON1 polymorphism and CVD are rather controversial. Some found positive association and others, among them one meta‐analysis study, did not find any association . There is also confirmatory evidence that low PON1 activity is positively associated with atherosclerosis, irrespective of PON1 genotype and/or activity phenotype .…”

Association between Paraoxonase-1 p.Q192R Polymorphism and Coronary Artery Disease susceptibility in the Colombian Population

“…10 The PON1 p. Q192R missense variant (c.575A>G, rs662) is the most extensively characterized PON1 SNP and has been associated with CAD susceptibility in numerous studies. [11][12][13][14][15][16][17][18][19] Intriguingly, other studies could not replicate this association, whereby the role of PON1 Q192R in CAD remains controversial. [20][21][22] PON1 is considered a key factor for the bioactivation and clinical activity of clopidogrel, an ADP P2Y12 receptor antagonist recommended as a first-line treatment for ACS.…”

“…Allelic and genotypic frequencies were obtained from numerous studies for comparisons. [11][12][13][14][15][16][17][18][19][20][21][22][33][34][35][36][37][38][39][40][41] The P value for significance was set at < 0.05. Analyses were conducted using R v4.0.3 (R Core Team, 2014) or SPSS v26 208 software (IBM Analytics).…”

Paraoxonase 1 gene variants concerning cardiovascular mortality in conventional cigarette smokers and non-smokers treated with hemodialysis

“…On the other hand, smokers with the rs662 GG genotype showed a higher atherogenic index and Framingham risk score than smoking and non-smoking AA + AG carriers. The rs662 GG genotype was discussed as associated with low arylesterase activity 23 . As one can see, the mentioned above data also do not provide thoroughly consistent results.…”

Serum Paraoxonase-1 Activity and Paraoxonase Q192 Gene Polymorphism in a Young, Healthy Population

“…PON1 gene polymorphisms independently influence the ability of the enzyme to protect LDL oxidation or alter PON1 activity (9). Although people with PON1 gene Q192R polymorphism are expected to be at an increased risk of CAD, literature reports conflicting data on the relationship of this polymorphism with endothelial dysfunction or coronary heart disease (8,(10)(11)(12)(13)(14). Serum lipid fractions and lipoprotein-related enzyme activities might differ between the populations.…”