PON1 polymorphisms are predictors of ability to attain HDL-C goals in statin-treated patients

Souza, Jéssica Aguiar de; Menin, A; Lima, Luciana Otero; Smiderle, Lisiane; Hutz, Mara H.; Sand, Cézar Roberto Van der; Sand, Luiz Carlos Van der; Ferreira, Maria Elvira Wagner; Pires, Renan Canibal; Almeida, Silvana; Fiegenbaum, Marilu

doi:10.1016/j.clinbiochem.2015.06.009

Cited by 8 publications

(7 citation statements)

References 49 publications

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“…de Souza et al studied the correlation between the Q192R (rs662) and L55M (rs854560) polymorphisms and statin responses in 433 dyslipidemic subjects who used statin lipidlowering therapy. Although the studied polymorphisms were not correlated with baseline lipid levels, both RR (χ(2) p = 0.009) and LL (χ(2) p = 0.026) homozygotes were underrepresented among those subjects that achieved their respective lipid goals, meaning that both polymorphisms may lead to interindividual variation in statin treatment response (de Souza et al, 2015).…”

Section: Paraoxonase 1 Gene Polymorphisms and Cardiovascular Diseasementioning

confidence: 89%

Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development

Vavlukis

Krsteva

et al. 2022

Front. Genet.

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Paraoxonase 1 (PON1) is calcium-dependent aryldialkylphosphatase, thought to possess; anti-oxidant, anti-adhesion, anti-inflammatory, anti-thrombosis and anti-apoptosis effects, as well as lipid-modifying properties. Numerous clinical studies have shown associations between different PON1 polymorphisms and different cardiovascular pathologies. The rs622 (c.575A > G) and the rs854560 (c.163A > T) are the most studied PON1 SNPs in the coding region, with rs705381 (− 162A/G), rs854572 (− 909G/C) and rs705379 (− 108C/T) being the most studied SNPs in the regulatory PON1 gene region. The three major PON1 activities are aryldialkylphosphatase, arylesterase and lactonase activity. The different SNPs affect PON1 serum concentrations and enzyme activity, thus leading to pro-/anti-atherogenic effects. In that setting, it is very difficult to establish as to whether the genotype or phenotype of PON1 is primarily associated with cardiovascular risk. Given the current scientific evidence, PON1 genotyping might be reasonable in patients with high and very high cardiovascular risk.

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Section: Paraoxonase 1 Gene Polymorphisms and Cardiovascular Diseasementioning

confidence: 89%

Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development

Vavlukis

Krsteva

et al. 2022

Front. Genet.

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“…The polymorphisms c.575A>G (Gln192Arg) and c.163T>A (Leu55Met) in the PON1 were studied in a sample of Brazilian HC subjects. Carriers of PON1 192Arg and 55Met alleles are more likely of achieving HDL cholesterol goals after long term treatment with simvastatin and atorvastatin (OR: 2.81, CI95%:1.35-5.85, P =0.006) (De Souza et al, 2015). On the other hand PON1 Gln192Arg was not associated with differences in plasma tocopherol and oxidative stress biomarkers, in HC subjects treated with simvastatin or atorvastatin for six months (Botelho et al, 2012).…”

Section: Reverse Cholesterol Transport-related Genesmentioning

confidence: 92%

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Hirata

Cerda

Genvigir

et al. 2018

Braz. J. Pharm. Sci.

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Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes lifestyle interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipidlowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population.

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“…As far as PON1 polymorphism is considered, studies showed a positive effect on HDL with pravastatin in an R allele carrier than QQ homozygous, and better levels in RR homozygous during simvastatin therapy. DE Souza et al had a different outcome with RR carriers who did not reach the HDL target as easily as those with the Q allele [ 83 ]. Clopidogrel, an antiplatelet therapy, used in the prevention and treatment of patients who undergo coronary angiography with stent implantation, has been a controversial study.…”

Section: Paraoxonase 1 and Its Implications In Various Diseasesmentioning

confidence: 99%

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

Sirca,

Mureșan,

Pallag

et al. 2024

IJMS

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The incidence and prevalence of cardiovascular diseases are still rising. The principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia and a pro-inflammatory state. Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 binds with HDL (high-density lipoprotein), and high serum levels lead to a protective state against dyslipidemia, cardiovascular diseases, diabetes, stroke, nonalcoholic fatty liver disease, and many others. Modulating PON1 expression might be a treatment objective with significant results in limiting the prevalence of atherosclerosis. Lifestyle including diet and exercise can raise its levels, and some beneficial plants have been found to influence PON1 levels; therefore, more studies on herbal components are needed. Our purpose is to highlight the principal roles of Praoxonase 1, its implications in dyslipidemia, cardiovascular diseases, stroke, and other diseases, and to emphasize plants that can modulate PON1 expression, targeting the potential of some flavonoids that could be introduced as supplements in our diet and to validate the hypothesis that flavonoids have any effects regarding PON1 function.

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PON1 polymorphisms are predictors of ability to attain HDL-C goals in statin-treated patients

Cited by 8 publications

References 49 publications

Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development

Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

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