CYBA C242T gene polymorphism and flow-mediated vasodilation in a population of young adults: the Cardiovascular Risk in Young Finns Study.
OBJECTIVE
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion that contributes to decreased nitric oxide bioavailability in the vasculature. The C242T polymorphism of the CYBA gene that encodes p22phox, a component of NADPH oxidase, has been found to modulate superoxide production. We examined the relationship of the C242T polymorphism with endothelial-dependent brachial artery flow-mediated vasodilatation (FMD) in a population-based sample of young healthy adults.


METHODS
FMD, defined as the increased percentage in brachial artery diameter after reactive hyperemia, was assessed by ultrasound and the C242T polymorphism using a 5' nuclease assay in 2058 subjects aged 24-39 years.


RESULTS
The mean values of brachial artery FMD were 8.0 +/- 4.4% in all study subjects (n = 2058), and 7.8 +/- 4.4, 8.2 +/- 4.5, and 8.7 +/- 4.5% in subjects with the CC (n = 1362), CT (n = 616), and TT (n = 80) genotypes of the C242T CYBA polymorphism, respectively (P = 0.02 for trend). The association remained significant (P = 0.019) in multivariate analyses adjusted for age, sex, obesity indices, smoking habits, blood pressure, serum glucose, lipids, and C-reactive protein. The relationship between FMD and the C242T polymorphism was stronger (P = 0.004) in overweight subjects (body mass index > or = 25 kg/m, n = 895) and ever-smokers (P = 0.008, n = 1082), whereas no relationship was found in normal-weight subjects and non-smokers (P = 0.824 and P = 0.438, respectively).


CONCLUSIONS
The C242T polymorphism of the CYBA gene seems to be related to endothelial function in a population-based sample of young healthy adults. Overweight and smoking status may modify this genetic effect.
Fan
Meng
M
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Finland. meng.fan@uta.fi
Raitakari
Olli T
OT
Kähönen
Mika
M
Juonala
Markus
M
Hutri-Kähönen
Nina
N
Marniemi
Jukka
J
Rontu
Riikka
R
Pörsti
Ilkka
I
Viikari
Jorma
J
Lehtimäki
Terho
T
D000328:Adult; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D006940:Hyperemia / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012039:Regional Blood Flow; D012307:Risk Factors; D014463:Ultrasonography; D014664:Vasodilation / Q000235:genetics*
D019255:NADPH Oxidases; C086986:CYBA protein, human