Paraoxonase 1 polymorphisms within a Mississippi USA population as possible biomarkers of enzyme activities associated with disease susceptibility

Biochem Genet. 2014 Dec;52(11-12):509-23. doi: 10.1007/s10528-014-9663-8. Epub 2014 Jul 16.

Abstract

Paraoxonase (PON1) hydrolyzes paraoxon (PO) and diazoxon (DZO), active metabolites of insecticides parathion and diazinon. The PON1 gene has single nucleotide polymorphisms (SNPs) including a codon 192 arginine (R) to glutamine (Q) and methionine (M) to leucine (L) at codon 55. Hydrolysis of PO (POase), DZO (DZOase), dihydrocoumarin (lactonase), and phenyl acetate (arylesterase) were evaluated for associations with race, gender, age, and PON1 55/192 SNP genotypes. Variables were analyzed both individually and in combination. QQ individuals had higher lactonase (p < 0.001) than RR individuals. This might partially explain why predominantly RR African Americans have higher rates of coronary disease than predominantly QQ Caucasians. Significant (p < 0.001) differences in arylesterase were seen among genotypes with QQ and MM lowest whereas RR and LL were highest. This opposes the prevailing belief that arylesterase is unaffected by genotype and suggests that this activity cannot be used to quantify PON1 protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetates / chemistry
  • Aged
  • Aryldialkylphosphatase / chemistry
  • Aryldialkylphosphatase / genetics*
  • Black or African American
  • Coronary Artery Disease / ethnology
  • Coronary Artery Disease / genetics*
  • Coumarins / chemistry
  • Female
  • Genetic Association Studies
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Mississippi
  • Organophosphorus Compounds / chemistry
  • Paraoxon / chemistry
  • Phenols / chemistry
  • Polymorphism, Single Nucleotide*
  • White People

Substances

  • Acetates
  • Coumarins
  • Genetic Markers
  • Organophosphorus Compounds
  • Phenols
  • phenyl acetate
  • diazoxon
  • Aryldialkylphosphatase
  • 3,4-dihydrocoumarin
  • Paraoxon