NAD(P)H oxidase p22phox Gene C242T polymorphism and lipoprotein oxidation

Clin Chim Acta. 2003 Sep;335(1-2):101-7. doi: 10.1016/s0009-8981(03)00284-5.

Abstract

Background: Vascular NAD(P)H oxidase is a key enzyme of superoxide anion production in human vessel walls. The C242T mutation in the CYBA gene coding for p22phox, a component of the enzyme, may change the redox state. The aim of this study was to evaluate the influence of the polymorphism on serum concentrations of oxidative stress markers.

Methods: Serum samples were collected from 134 Type 2 diabetic patients and analyzed for oxidized high-density lipoprotein (HDL) by in-house ELISA, and oxidized low-density lipoprotein (LDL) and thiobarbituric acid reactive substance (TBARS) by commercial kits. For genotyping, the Taqman PCR method was adapted to detect the polymorphism.

Results: Circulating concentrations of oxidized HDL were about 1.5-fold lower in those of the CT/TT genotypes than the CC genotype [3.3 +/- 0.3 and 5.0 +/- 0.3 U/dl (mean +/- S.E.M.), respectively; multiple regression analysis, p=0.006], whereas concentrations of oxidized LDL were slightly greater (1.1-fold, p=0.01) in those with the CT/TT genotypes. However, no significant difference was observed in TBARS between the genotypes.

Conclusions: The effect was inconsistent among the markers, but these results suggest that the CYBA C242T polymorphism is involved in NAD(P)H oxidase activity and affects oxidation of lipoproteins by altering the redox state in the vasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / enzymology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genotype
  • Humans
  • Japan
  • Lipoproteins / blood*
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / metabolism
  • Male
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Middle Aged
  • Mutation
  • NADPH Dehydrogenase / genetics*
  • NADPH Dehydrogenase / metabolism
  • NADPH Oxidases
  • Oxidation-Reduction
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Superoxides / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Lipoproteins
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Membrane Transport Proteins
  • Phosphoproteins
  • Thiobarbituric Acid Reactive Substances
  • Superoxides
  • NADPH Oxidases
  • CYBA protein, human
  • NADPH Dehydrogenase