NAD(P)H oxidase p22phox Gene C242T polymorphism and lipoprotein oxidation.
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.
Nakano
Takanari
T
Immunology Laboratory, Diagnostics Department, YAMASA Corporation, 2-10-1 Araoi-cho, Choshi, Chiba 288-0056, Japan. nakano@yamasa.com
Matsunaga
Seiko
S
Nagata
Atsuo
A
Maruyama
Taro
T
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009252:NADPH Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D019255:NADPH Oxidases; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase