p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

Arq Bras Cardiol. 2015 Jul;105(1):45-52. doi: 10.5935/abc.20150053. Epub 2015 May 29.
[Article in English, Portuguese]

Abstract

Background: Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL).

Objective: To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.

Methods: We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317).

Results: The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques.

Conclusion: In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aryldialkylphosphatase / blood
  • Aryldialkylphosphatase / genetics*
  • Brazil
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / ethnology
  • Carotid Artery Diseases / genetics*
  • Carotid Intima-Media Thickness
  • Female
  • Genetic Association Studies
  • Humans
  • Lipoproteins / blood
  • Lipoproteins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Real-Time Polymerase Chain Reaction
  • Reference Values
  • Regression Analysis
  • Risk Factors
  • Young Adult

Substances

  • Lipoproteins
  • Aryldialkylphosphatase
  • PON1 protein, human