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

Jéssica Aguiar de Souza1, Angelica Menin1, Luciana Otero Lima2

  • 1Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Rio Grande do Sul, Brazil.

Clinical Biochemistry
|June 17, 2015
PubMed

Insights

Genetic variations in the PON1 gene (Q192R and L55M) influence high-density lipoprotein cholesterol (HDL-C) goal attainment in patients treated with statins. These PON1 polymorphisms may predict individual responses to statin therapy for cardiovascular disease prevention.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Disease Research
  • Lipid Metabolism

Background:

  • Paraoxonase 1 (PON1) inhibits LDL-C oxidation, crucial for preventing atherosclerosis.
  • While PON1 influences HDL-C, its genetic variations' impact on HDL-C levels and statin response remains debated.
  • Understanding these genetic factors is key to personalized cardiovascular risk management.

Purpose of the Study:

  • To investigate the association between two PON1 gene polymorphisms (Q192R and L55M) and patient response to statin therapy.
  • To determine if these genetic variations affect the achievement of high-density lipoprotein cholesterol (HDL-C) goals.
  • To analyze statin response in a South Brazilian population with dyslipidemia.

Main Methods:

  • A cohort of 433 dyslipidemic patients receiving statins (simvastatin/atorvastatin) was studied.
  • Lipid profiles (Total Cholesterol, Triglyceride, HDL-C, LDL-C) were measured pre- and post-treatment (approx. 6 months).
  • Real-time PCR was used to genotype PON1 Q192R (rs662) and L55M (rs854560) polymorphisms.

Main Results:

  • No association was found between baseline lipid levels and the Q192R or L55M polymorphisms.
  • Patients with Q192R RR homozygosity and L55M LL homozygosity were less likely to achieve HDL-C goals.
  • Carriers of QQ/QR genotypes for Q192R and MM/ML genotypes for L55M showed an increased chance of attaining HDL-C goals.
  • Multivariate analysis identified gender, baseline HDL-C, and combined PON1 genotypes as predictors of achieving HDL-C goals.

Conclusions:

  • The Q192R (rs662) and L55M (rs854560) polymorphisms in the PON1 gene are associated with variations in achieving HDL-C goals during statin treatment.
  • These findings suggest that PON1 genotype may influence individual responses to statins, impacting cardiovascular disease management.
  • Further research can explore incorporating these genetic markers for personalized statin therapy selection.
Abstract

Keywords:
DyslipidemiaHDL-CLDL-CPON1ParaoxonaseStatins

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