Insight into the role of CYBA A640G and C242T gene variants and coronary heart disease risk. A case-control study.
The CYBA gene variants have been inconsistently associated with coronary heart disease (CHD) risk. A case-control study was conducted genotyping 619 subjects to explore the contribution of C242T and A640G to CHD risk in the population. A significant risk was found associated with GG homozygosity (odds ratio (OR) 2.132, 95% confidence interval, 1.113-4.085). The C242T variant was associated with CHD risk in women. Bias due to population stratification was analysed. Phenotype changes linked to these polymorphisms were evaluated. Superoxide measurements revealed higher production as indicated by the presence of the G and T alleles. Differences in mRNA concentration in heterozygous A640G samples were analysed. Higher levels of G allele mRNA compared with A allele mRNA were found. NAD(P)H oxidase p22phox sub-unit expression was evaluated with Western blot. Experiments revealed a gradual relationship in p22phox protein expression according to genotypes of the analysed variants. Those GG TT double homozygous showed increased p22phox protein expressions regarding AA CC double homozygous. This study has demonstrated increased expression and activity of the NAD(P)H system components during atherogenesis and the results could help explain the relevance of the A640G variant as a CHD marker.
Macías-Reyes
A
A
Research Unit, HUGC Dr. Negrín, Las Palmas de Gran Canaria, Spain.
Rodríguez-Esparragón
F
F
Caballero-Hidalgo
A
A
Hernández-Trujillo
Y
Y
Medina
A
A
Rodríguez-Pérez
J C
JC
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003327:Coronary Disease / Q000201:enzymology / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008323:Mammary Arteries / Q000201:enzymology; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013030:Spain; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
D008054:Lipid Peroxides; D012333:RNA, Messenger; D013481:Superoxides; D019255:NADPH Oxidases; C086986:CYBA protein, human